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1. Author Correction: Integrative genetic analysis illuminates ALS heritability and identifies risk genes

Author: Megat, Salim, Mora, Natalia, Sanogo, Jason, Roman, Olga, Catanese, Alberto, Alami, Najwa Ouali, Freischmidt, Axel, Mingaj, Xhuljana, De Calbiac, Hortense, Muratet, François, Dirrig-Grosch, Sylvie, Dieterle, Stéphane, Van Bakel, Nick, Müller, Kathrin, Sieverding, Kirsten, Weishaupt, Jochen, Andersen, Peter Munch, Weber, Markus, Neuwirth, Christoph, Margelisch, Markus, Sommacal, Andreas, Van Eijk, Kristel R., Veldink, Jan H., Lautrette, Géraldine, Couratier, Philippe, Camuzat, Agnès, Le Ber, Isabelle, Grassano, Maurizio, Chio, Adriano, Boeckers, Tobias, Ludolph, Albert C., Roselli, Francesco, Yilmazer-Hanke, Deniz, Millecamps, Stéphanie, Kabashi, Edor, Storkebaum, Erik, Sellier, Chantal, and Dupuis, Luc
Published: 2023
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2. Integrative genetic analysis illuminates ALS heritability and identifies risk genes

Author: Megat, Salim, Mora, Natalia, Sanogo, Jason, Roman, Olga, Catanese, Alberto, Alami, Najwa Ouali, Freischmidt, Axel, Mingaj, Xhuljana, De Calbiac, Hortense, Muratet, François, Dirrig-Grosch, Sylvie, Dieterle, Stéphane, Van Bakel, Nick, Müller, Kathrin, Sieverding, Kirsten, Weishaupt, Jochen, Andersen, Peter Munch, Weber, Markus, Neuwirth, Christoph, Margelisch, Markus, Sommacal, Andreas, Van Eijk, Kristel R., Veldink, Jan H., Lautrette, Géraldine, Couratier, Philippe, Camuzat, Agnès, Le Ber, Isabelle, Grassano, Maurizio, Chio, Adriano, Boeckers, Tobias, Ludolph, Albert C., Roselli, Francesco, Yilmazer-Hanke, Deniz, Millecamps, Stéphanie, Kabashi, Edor, Storkebaum, Erik, Sellier, Chantal, and Dupuis, Luc
Published: 2023
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3. Author Correction: Integrative genetic analysis illuminates ALS heritability and identifies risk genes

Author: Salim Megat, Natalia Mora, Jason Sanogo, Olga Roman, Alberto Catanese, Najwa Ouali Alami, Axel Freischmidt, Xhuljana Mingaj, Hortense De Calbiac, François Muratet, Sylvie Dirrig-Grosch, Stéphane Dieterle, Nick Van Bakel, Kathrin Müller, Kirsten Sieverding, Jochen Weishaupt, Peter Munch Andersen, Markus Weber, Christoph Neuwirth, Markus Margelisch, Andreas Sommacal, Kristel R. Van Eijk, Jan H. Veldink, Project Mine Als Sequencing Consortium, Géraldine Lautrette, Philippe Couratier, Agnès Camuzat, Isabelle Le Ber, Maurizio Grassano, Adriano Chio, Tobias Boeckers, Albert C. Ludolph, Francesco Roselli, Deniz Yilmazer-Hanke, Stéphanie Millecamps, Edor Kabashi, Erik Storkebaum, Chantal Sellier, and Luc Dupuis
Subjects: Science
Published: 2023
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4. Homozygous GRN mutations: unexpected phenotypes and new insights into pathological and molecular mechanisms

Author: Huin, Vincent, Barbier, Mathieu, Bottani, Armand, Lobrinus, Johannes, Clot, Fabienne, Lamari, Foudil, Chat, Laureen, Rucheton, Benoît, Fluchère, Frédérique, Auvin, Stéphane, Myers, Peter, Gelot, Antoinette, Camuzat, Agnès, Caillaud, Catherine, Jornéa, Ludmila, Forlani, Sylvie, Saracino, Dario, Duyckaerts, Charles, Brice, Alexis, Durr, Alexandra, and Ber, Isabelle Le
Subjects: Quantitative Biology - Biomolecules, Quantitative Biology - Genomics, Quantitative Biology - Neurons and Cognition
Abstract: Homozygous mutations in the progranulin gene (GRN) are associated with neuronal ceroid lipofuscinosis 11 (CLN11), a rare lysosomal-storage disorder characterized by cerebellar ataxia, seizures, retinitis pigmentosa, and cognitive disorders, usually beginning between 13 and 25 years of age. This is a rare condition, previously reported in only four families. In contrast, heterozygous GRN mutations are a major cause of frontotemporal dementia associated with neuronal cytoplasmic TDP-43 inclusions. We identified homozygous GRN mutations in six new patients. The phenotypic spectrum is much broader than previously reported, with two remarkably distinct presentations, depending on the age of onset. A childhood/juvenile form is characterized by classical CLN11 symptoms at an early age at onset. Unexpectedly, other homozygous patients presented a distinct delayed phenotype of frontotemporal dementia and parkinsonism after 50 years; none had epilepsy or cerebellar ataxia. Another major finding of this study is that all GRN mutations may not have the same impact on progranulin protein synthesis. A hypomorphic effect of some mutations is supported by the presence of residual levels of plasma progranulin and low levels of normal transcript detected in one case with a homozygous splice-site mutation and late onset frontotemporal dementia. This is a new critical finding that must be considered in therapeutic trials based on replacement strategies. The first neuropathological study in a homozygous carrier provides new insights into the pathological mechanisms of the disease. Hallmarks of neuronal ceroid lipofuscinosis were present. The absence of TDP-43 cytoplasmic inclusions markedly differs from observations of heterozygous mutations, suggesting a pathological shift between lysosomal and TDP-43 pathologies depending on the mono or bi-allelic status. An intriguing observation was the loss of normal TDP-43 staining in the nucleus of some neurons, which could be the first stage of the TDP-43 pathological process preceding the formation of typical cytoplasmic inclusions. Finally, this study has important implications for genetic counselling and molecular diagnosis. Semi-dominant inheritance of GRN mutations implies that specific genetic counseling should be delivered to children and parents of CLN11 patients, as they are heterozygous carriers with a high risk of developing dementia. More broadly, this study illustrates the fact that genetic variants can lead to different phenotypes according to their mono- or bi-allelic state, which is a challenge for genetic diagnosis.
Published: 2020
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5. Prodromal language impairment in genetic frontotemporal dementia within the GENFI cohort

Author: Nelson, Annabel, Thomas, David L., Todd, Emily, Benotmane, Hanya, Nicholas, Jennifer, Shafei, Rachelle, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Papma, Janne M., Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B., Miltenberger, Gabriel, do Couto, Frederico Simões, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Samra, Kiran, MacDougall, Amy M., Bouzigues, Arabella, Bocchetta, Martina, Cash, David M., Greaves, Caroline V., Convery, Rhian S., van Swieten, John C., Jiskoot, Lize, Seelaar, Harro, Moreno, Fermin, Sanchez-Valle, Raquel, Laforce, Robert, Graff, Caroline, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B., Borroni, Barbara, Finger, Elizabeth, Synofzik, Matthis, Galimberti, Daniela, Vandenberghe, Rik, de Mendonça, Alexandre, Butler, Chris R., Gerhard, Alex, Ducharme, Simon, Le Ber, Isabelle, Tiraboschi, Pietro, Santana, Isabel, Pasquier, Florence, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Rohrer, Jonathan D., and Russell, Lucy L.
Published: 2023
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6. Age at symptom onset and death and disease duration in genetic frontotemporal dementia: an international retrospective cohort study.

Author: Moore, Katrina M, Nicholas, Jennifer, Grossman, Murray, McMillan, Corey T, Irwin, David J, Massimo, Lauren, Van Deerlin, Vivianna M, Warren, Jason D, Fox, Nick C, Rossor, Martin N, Mead, Simon, Bocchetta, Martina, Boeve, Bradley F, Knopman, David S, Graff-Radford, Neill R, Forsberg, Leah K, Rademakers, Rosa, Wszolek, Zbigniew K, van Swieten, John C, Jiskoot, Lize C, Meeter, Lieke H, Dopper, Elise Gp, Papma, Janne M, Snowden, Julie S, Saxon, Jennifer, Jones, Matthew, Pickering-Brown, Stuart, Le Ber, Isabelle, Camuzat, Agnès, Brice, Alexis, Caroppo, Paola, Ghidoni, Roberta, Pievani, Michela, Benussi, Luisa, Binetti, Giuliano, Dickerson, Bradford C, Lucente, Diane, Krivensky, Samantha, Graff, Caroline, Öijerstedt, Linn, Fallström, Marie, Thonberg, Håkan, Ghoshal, Nupur, Morris, John C, Borroni, Barbara, Benussi, Alberto, Padovani, Alessandro, Galimberti, Daniela, Scarpini, Elio, Fumagalli, Giorgio G, Mackenzie, Ian R, Hsiung, Ging-Yuek R, Sengdy, Pheth, Boxer, Adam L, Rosen, Howie, Taylor, Joanne B, Synofzik, Matthis, Wilke, Carlo, Sulzer, Patricia, Hodges, John R, Halliday, Glenda, Kwok, John, Sanchez-Valle, Raquel, Lladó, Albert, Borrego-Ecija, Sergi, Santana, Isabel, Almeida, Maria Rosário, Tábuas-Pereira, Miguel, Moreno, Fermin, Barandiaran, Myriam, Indakoetxea, Begoña, Levin, Johannes, Danek, Adrian, Rowe, James B, Cope, Thomas E, Otto, Markus, Anderl-Straub, Sarah, de Mendonça, Alexandre, Maruta, Carolina, Masellis, Mario, Black, Sandra E, Couratier, Philippe, Lautrette, Geraldine, Huey, Edward D, Sorbi, Sandro, Nacmias, Benedetta, Laforce, Robert, Tremblay, Marie-Pier L, Vandenberghe, Rik, Damme, Philip Van, Rogalski, Emily J, Weintraub, Sandra, Gerhard, Alexander, Onyike, Chiadi U, Ducharme, Simon, Papageorgiou, Sokratis G, Ng, Adeline Su Lyn, Brodtmann, Amy, Finger, Elizabeth, and Guerreiro, Rita
Subjects: FTD Prevention Initiative, Humans, Disease Progression, tau Proteins, Retrospective Studies, Cohort Studies, Family, Age of Onset, Phenotype, Mutation, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Frontotemporal Dementia, C9orf72 Protein, Progranulins, Clinical Research, Rare Diseases, Dementia, Aging, Brain Disorders, Genetic Testing, Neurodegenerative, Neurosciences, Alzheimer's Disease Related Dementias (ADRD), Prevention, Genetics, Acquired Cognitive Impairment, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), 2.1 Biological and endogenous factors, Neurological, Neurology & Neurosurgery, Clinical Sciences
Abstract: BackgroundFrontotemporal dementia is a heterogenous neurodegenerative disorder, with about a third of cases being genetic. Most of this genetic component is accounted for by mutations in GRN, MAPT, and C9orf72. In this study, we aimed to complement previous phenotypic studies by doing an international study of age at symptom onset, age at death, and disease duration in individuals with mutations in GRN, MAPT, and C9orf72.MethodsIn this international, retrospective cohort study, we collected data on age at symptom onset, age at death, and disease duration for patients with pathogenic mutations in the GRN and MAPT genes and pathological expansions in the C9orf72 gene through the Frontotemporal Dementia Prevention Initiative and from published papers. We used mixed effects models to explore differences in age at onset, age at death, and disease duration between genetic groups and individual mutations. We also assessed correlations between the age at onset and at death of each individual and the age at onset and at death of their parents and the mean age at onset and at death of their family members. Lastly, we used mixed effects models to investigate the extent to which variability in age at onset and at death could be accounted for by family membership and the specific mutation carried.FindingsData were available from 3403 individuals from 1492 families: 1433 with C9orf72 expansions (755 families), 1179 with GRN mutations (483 families, 130 different mutations), and 791 with MAPT mutations (254 families, 67 different mutations). Mean age at symptom onset and at death was 49·5 years (SD 10·0; onset) and 58·5 years (11·3; death) in the MAPT group, 58·2 years (9·8; onset) and 65·3 years (10·9; death) in the C9orf72 group, and 61·3 years (8·8; onset) and 68·8 years (9·7; death) in the GRN group. Mean disease duration was 6·4 years (SD 4·9) in the C9orf72 group, 7·1 years (3·9) in the GRN group, and 9·3 years (6·4) in the MAPT group. Individual age at onset and at death was significantly correlated with both parental age at onset and at death and with mean family age at onset and at death in all three groups, with a stronger correlation observed in the MAPT group (r=0·45 between individual and parental age at onset, r=0·63 between individual and mean family age at onset, r=0·58 between individual and parental age at death, and r=0·69 between individual and mean family age at death) than in either the C9orf72 group (r=0·32 individual and parental age at onset, r=0·36 individual and mean family age at onset, r=0·38 individual and parental age at death, and r=0·40 individual and mean family age at death) or the GRN group (r=0·22 individual and parental age at onset, r=0·18 individual and mean family age at onset, r=0·22 individual and parental age at death, and r=0·32 individual and mean family age at death). Modelling showed that the variability in age at onset and at death in the MAPT group was explained partly by the specific mutation (48%, 95% CI 35-62, for age at onset; 61%, 47-73, for age at death), and even more by family membership (66%, 56-75, for age at onset; 74%, 65-82, for age at death). In the GRN group, only 2% (0-10) of the variability of age at onset and 9% (3-21) of that of age of death was explained by the specific mutation, whereas 14% (9-22) of the variability of age at onset and 20% (12-30) of that of age at death was explained by family membership. In the C9orf72 group, family membership explained 17% (11-26) of the variability of age at onset and 19% (12-29) of that of age at death.InterpretationOur study showed that age at symptom onset and at death of people with genetic frontotemporal dementia is influenced by genetic group and, particularly for MAPT mutations, by the specific mutation carried and by family membership. Although estimation of age at onset will be an important factor in future pre-symptomatic therapeutic trials for all three genetic groups, our study suggests that data from other members of the family will be particularly helpful only for individuals with MAPT mutations. Further work in identifying both genetic and environmental factors that modify phenotype in all groups will be important to improve such estimates.FundingUK Medical Research Council, National Institute for Health Research, and Alzheimer's Society.
Published: 2020

7. Integrative genetic analysis illuminates ALS heritability and identifies risk genes

Author: Salim Megat, Natalia Mora, Jason Sanogo, Olga Roman, Alberto Catanese, Najwa Ouali Alami, Axel Freischmidt, Xhuljana Mingaj, Hortense De Calbiac, François Muratet, Sylvie Dirrig-Grosch, Stéphane Dieterle, Nick Van Bakel, Kathrin Müller, Kirsten Sieverding, Jochen Weishaupt, Peter Munch Andersen, Markus Weber, Christoph Neuwirth, Markus Margelisch, Andreas Sommacal, Kristel R. Van Eijk, Jan H. Veldink, Project Mine Als Sequencing Consortium, Géraldine Lautrette, Philippe Couratier, Agnès Camuzat, Isabelle Le Ber, Maurizio Grassano, Adriano Chio, Tobias Boeckers, Albert C. Ludolph, Francesco Roselli, Deniz Yilmazer-Hanke, Stéphanie Millecamps, Edor Kabashi, Erik Storkebaum, Chantal Sellier, and Luc Dupuis
Subjects: Science
Abstract: Abstract Amyotrophic lateral sclerosis (ALS) has substantial heritability, in part shared with fronto-temporal dementia (FTD). We show that ALS heritability is enriched in splicing variants and in binding sites of 6 RNA-binding proteins including TDP-43 and FUS. A transcriptome wide association study (TWAS) identified 6 loci associated with ALS, including in NUP50 encoding for the nucleopore basket protein NUP50. Independently, rare variants in NUP50 were associated with ALS risk (P = 3.71.10−03; odds ratio = 3.29; 95%CI, 1.37 to 7.87) in a cohort of 9,390 ALS/FTD patients and 4,594 controls. Cells from one patient carrying a NUP50 frameshift mutation displayed a decreased level of NUP50. Loss of NUP50 leads to death of cultured neurons, and motor defects in Drosophila and zebrafish. Thus, our study identifies alterations in splicing in neurons as critical in ALS and provides genetic evidence linking nuclear pore defects to ALS.
Published: 2023
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8. Early neurotransmitters changes in prodromal frontotemporal dementia: A GENFI study

Author: Esteve, Aitana Sogorb, Heller, Carolin, Greaves, Caroline V., Zetterberg, Henrik, Swift, Imogen J., Samra, Kiran, Shafei, Rachelle, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Tiraboschi, Pietro, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Papma, Janne M., Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B., Miltenberger, Gabriel, do Couto, Frederico Simões, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Premi, Enrico, Pengo, Marta, Mattioli, Irene, Cantoni, Valentina, Dukart, Juergen, Gasparotti, Roberto, Buratti, Emanuele, Padovani, Alessandro, Bocchetta, Martina, Todd, Emily G., Bouzigues, Arabella, Cash, David M., Convery, Rhian S., Russell, Lucy L., Foster, Phoebe, Thomas, David L., van Swieten, John C., Jiskoot, Lize C., Seelaar, Harro, Galimberti, Daniela, Sanchez-Valle, Raquel, Laforce, Robert, Jr, Moreno, Fermin, Synofzik, Matthis, Graff, Caroline, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B., Tsvetanov, Kamen A., Vandenberghe, Rik, Finger, Elizabeth, de Mendonça, Alexandre, Santana, Isabel, Butler, Chris R., Ducharme, Simon, Gerhard, Alexander, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Le Ber, Isabelle, Pasquier, Florence, Rohrer, Jonathan D., and Borroni, Barbara
Published: 2023
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9. MicroRNA signatures in genetic frontotemporal dementia and amyotrophic lateral sclerosis

Author: Virgilio Kmetzsch, Morwena Latouche, Dario Saracino, Daisy Rinaldi, Agnès Camuzat, Thomas Gareau, the French Research Network on FTD/ALS, Isabelle Le Ber, Olivier Colliot, and Emmanuelle Becker
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Objective MicroRNAs are promising biomarkers of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), but discrepant results between studies have so far hampered their use in clinical trials. We aim to assess all previously identified circulating microRNA signatures as potential biomarkers of genetic FTD and/or ALS, using homogeneous, independent validation cohorts of C9orf72 and GRN mutation carriers. Methods 104 individuals carrying a C9orf72 or a GRN mutation, along with 31 controls, were recruited through the French research network on FTD/ALS. All subjects underwent blood sampling, from which circulating microRNAs were extracted. We measured differences in the expression levels of 65 microRNAs, selected from 15 published studies about FTD or ALS, between 31 controls, 17 C9orf72 presymptomatic subjects, and 29 C9orf72 patients. We also assessed differences in the expression levels of 30 microRNAs, selected from five studies about FTD, between 31 controls, 30 GRN presymptomatic subjects, and 28 GRN patients. Results More than half (35/65) of the selected microRNAs were differentially expressed in the C9orf72 cohort, while only a small proportion (5/30) of microRNAs were differentially expressed in the GRN cohort. In multivariate analyses, only individuals in the C9orf72 cohort could be adequately classified (ROC AUC up to 0.98 for controls versus presymptomatic subjects, 0.94 for controls versus patients, and 0.77 for presymptomatic subjects versus patients) with some of the signatures. Interpretation Our results suggest that previously identified microRNAs using sporadic or mixed cohorts of FTD and ALS patients could potentially serve as biomarkers of C9orf72‐associated disease, but not GRN‐associated disease.
Published: 2022
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10. C9ORF72 knockdown triggers FTD-like symptoms and cell pathology in mice

Author: Maria-Belen Lopez-Herdoiza, Stephanie Bauché, Baptiste Wilmet, Caroline Le Duigou, Delphine Roussel, Magali Frah, Jonas Béal, Gabin Devely, Susana Boluda, Petra Frick, Delphine Bouteiller, Sébastien Dussaud, Pierre Guillabert, Carine Dalle, Magali Dumont, Agnes Camuzat, Dario Saracino, Mathieu Barbier, Gaelle Bruneteau, Phillippe Ravassard, Manuela Neumann, Sophie Nicole, Isabelle Le Ber, Alexis Brice, and Morwena Latouche
Subjects: TDP-43, C9ORF72, FTD (frontotemporal dementia), ALS (amyotrophic lateral sclerosis), autophagy/lysosomal pathway, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: The GGGGCC intronic repeat expansion within C9ORF72 is the most common genetic cause of ALS and FTD. This mutation results in toxic gain of function through accumulation of expanded RNA foci and aggregation of abnormally translated dipeptide repeat proteins, as well as loss of function due to impaired transcription of C9ORF72. A number of in vivo and in vitro models of gain and loss of function effects have suggested that both mechanisms synergize to cause the disease. However, the contribution of the loss of function mechanism remains poorly understood. We have generated C9ORF72 knockdown mice to mimic C9-FTD/ALS patients haploinsufficiency and investigate the role of this loss of function in the pathogenesis. We found that decreasing C9ORF72 leads to anomalies of the autophagy/lysosomal pathway, cytoplasmic accumulation of TDP-43 and decreased synaptic density in the cortex. Knockdown mice also developed FTD-like behavioral deficits and mild motor phenotypes at a later stage. These findings show that C9ORF72 partial loss of function contributes to the damaging events leading to C9-FTD/ALS.
Published: 2023
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11. Early neurotransmitters changes in prodromal frontotemporal dementia: A GENFI study

Author: Enrico Premi, Marta Pengo, Irene Mattioli, Valentina Cantoni, Juergen Dukart, Roberto Gasparotti, Emanuele Buratti, Alessandro Padovani, Martina Bocchetta, Emily G. Todd, Arabella Bouzigues, David M. Cash, Rhian S. Convery, Lucy L. Russell, Phoebe Foster, David L. Thomas, John C. van Swieten, Lize C. Jiskoot, Harro Seelaar, Daniela Galimberti, Raquel Sanchez-Valle, Robert Laforce, Jr, Fermin Moreno, Matthis Synofzik, Caroline Graff, Mario Masellis, Maria Carmela Tartaglia, James B. Rowe, Kamen A. Tsvetanov, Rik Vandenberghe, Elizabeth Finger, Pietro Tiraboschi, Alexandre de Mendonça, Isabel Santana, Chris R. Butler, Simon Ducharme, Alexander Gerhard, Johannes Levin, Markus Otto, Sandro Sorbi, Isabelle Le Ber, Florence Pasquier, Jonathan D. Rohrer, Barbara Borroni, Aitana Sogorb Esteve, Carolin Heller, Caroline V. Greaves, Henrik Zetterberg, Imogen J. Swift, Kiran Samra, Rachelle Shafei, Carolyn Timberlake, Thomas Cope, Timothy Rittman, Andrea Arighi, Chiara Fenoglio, Elio Scarpini, Giorgio Fumagalli, Vittoria Borracci, Giacomina Rossi, Giorgio Giaccone, Giuseppe Di Fede, Paola Caroppo, Sara Prioni, Veronica Redaelli, David Tang-Wai, Ekaterina Rogaeva, Miguel Castelo-Branco, Morris Freedman, Ron Keren, Sandra Black, Sara Mitchell, Christen Shoesmith, Robart Bartha, Rosa Rademakers, Jackie Poos, Janne M. Papma, Lucia Giannini, Rick van Minkelen, Yolande Pijnenburg, Benedetta Nacmias, Camilla Ferrari, Cristina Polito, Gemma Lombardi, Valentina Bessi, Michele Veldsman, Christin Andersson, Hakan Thonberg, Linn Öijerstedt, Vesna Jelic, Paul Thompson, Tobias Langheinrich, Albert Lladó, Anna Antonell, Jaume Olives, Mircea Balasa, Nuria Bargalló, Sergi Borrego-Ecija, Ana Verdelho, Carolina Maruta, Catarina B. Ferreira, Gabriel Miltenberger, Frederico Simões do Couto, Alazne Gabilondo, Ana Gorostidi, Jorge Villanua, Marta Cañada, Mikel Tainta, Miren Zulaica, Myriam Barandiaran, Patricia Alves, Benjamin Bender, Carlo Wilke, Lisa Graf, Annick Vogels, Mathieu Vandenbulcke, Philip Van Damme, Rose Bruffaerts, Koen Poesen, Pedro Rosa-Neto, Serge Gauthier, Agnès Camuzat, Alexis Brice, Anne Bertrand, Aurélie Funkiewiez, Daisy Rinaldi, Dario Saracino, Olivier Colliot, Sabrina Sayah, Catharina Prix, Elisabeth Wlasich, Olivia Wagemann, Sandra Loosli, Sonja Schönecker, Tobias Hoegen, Jolina Lombardi, Sarah Anderl-Straub, Adeline Rollin, Gregory Kuchcinski, Maxime Bertoux, Thibaud Lebouvier, Vincent Deramecourt, Beatriz Santiago, Diana Duro, Maria João Leitão, Maria Rosario Almeida, Miguel Tábuas-Pereira, and Sónia Afonso
Subjects: Frontotemporal dementia, Frontotemporal lobar degeneration, Genes, Magnetic resonance imaging, Positron emission tomography, Neurotransmitters, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Background: Neurotransmitters deficits in Frontotemporal Dementia (FTD) are still poorly understood. Better knowledge of neurotransmitters impairment, especially in prodromal disease stages, might tailor symptomatic treatment approaches. Methods: In the present study, we applied JuSpace toolbox, which allowed for cross-modal correlation of Magnetic Resonance Imaging (MRI)-based measures with nuclear imaging derived estimates covering various neurotransmitter systems including dopaminergic, serotonergic, noradrenergic, GABAergic and glutamatergic neurotransmission.We included 392 mutation carriers (157 GRN, 164 C9orf72, 71 MAPT), together with 276 non-carrier cognitively healthy controls (HC). We tested if the spatial patterns of grey matter volume (GMV) alterations in mutation carriers (relative to HC) are correlated with specific neurotransmitter systems in prodromal (CDR® plus NACC FTLD = 0.5) and in symptomatic (CDR® plus NACC FTLD≥1) FTD. Results: In prodromal stages of C9orf72 disease, voxel-based brain changes were significantly associated with spatial distribution of dopamine and acetylcholine pathways; in prodromal MAPT disease with dopamine and serotonin pathways, while in prodromal GRN disease no significant findings were reported (p
Published: 2023
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12. Structural brain splitting is a hallmark of Granulin-related frontotemporal dementia

Author: Afonso, Sónia, Almeida, Maria Rosario, Andersson, Christin, Antonell, Anna, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Bertoux, Maxime, Bertrand, Anne, Bessi, Valentina, Black, Sandra, Borrego-Ecija, Sergi, Bouzigues, Arabella, Bras, Jose, Brice, Alexis, Bruffaerts, Rose, Camuzat, Agnès, Cañada, Marta, Cantoni, Valentina, Caroppo, Paola, Castelo-Branco, Miguel, Colliot, Olivier, Cope, Thomas, Deramecourt, Vincent, Fede, Giuseppe Di, Díez, Alina, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B., Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Funkiewiez, Aurélie, Gabilondo, Alazne, Gauthier, Serge, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Karnath, Hans-Otto, Keren, Ron, Kuchcinski, Gregory, Langheinrich, Tobias, Lebouvier, Thibaud, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Lombardi, Jolina, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, van Minkelen, Rick, Mitchell, Sara, Moore, Katrina, Nacmias, Benedetta, Nelson, Annabel, Nicholas, Jennifer, Öijerstedt, Linn, Olives, Jaume, Ourselin, Sebastien, Panman, Jessica, Papma, Janne M., Pijnenburg, Yolande, Polito, Cristina, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rinaldi, Daisy, Rittman, Tim, Rogaeva, Ekaterina, Rollin, Adeline, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Saracino, Dario, Sayah, Sabrina, Scarpini, Elio, Schönecker, Sonja, Shafei, Rachelle, Shoesmith, Christen, Swift, Imogen, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Tang-Wai, David, Thomas, David L, Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Van Damme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Gazzina, Stefano, Grassi, Mario, Premi, Enrico, Alberici, Antonella, Benussi, Alberto, Archetti, Silvana, Gasparotti, Roberto, Bocchetta, Martina, Cash, David M., Todd, Emily G., Peakman, Georgia, Convery, Rhian S., van Swieten, John C., Jiskoot, Lize C., Seelaar, Harro, Sanchez-Valle, Raquel, Moreno, Fermin, Laforce, Robert, Jr, Graff, Caroline, Synofzik, Matthis, Galimberti, Daniela, Rowe, James B., Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, Vandenberghe, Rik, de Mendonça, Alexandre, Tagliavini, Fabrizio, Butler, Chris R., Santana, Isabel, Gerhard, Alexander, Ber, Isabelle Le, Pasquier, Florence, Ducharme, Simon, Levin, Johannes, Danek, Adrian, Sorbi, Sandro, Otto, Markus, Rohrer, Jonathan D., and Borroni, Barbara
Published: 2022
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13. Examining empathy deficits across familial forms of frontotemporal dementia within the GENFI cohort

Author: Afonso, Sónia, Almeida, Maria Rosario, Anderl-Straub, Sarah, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Bertoux, Maxime, Bertrand, Anne, Bessi, Valentina, Black, Sandra, Borrego-Ecija, Sergi, Bras, Jose, Brice, Alexis, Bruffaerts, Rose, Camuzat, Agnès, Cañada, Marta, Cantoni, Valentina, Caroppo, Paola, Cash, David, Castelo-Branco, Miguel, Colliot, Olivier, Cope, Thomas, Deramecourt, Vincent, de Arriba, María, Di Fede, Giuseppe, Díez, Alina, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B., Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Funkiewiez, Aurélie, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, Gazzina, Stefano, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Karnath, Hans-Otto, Keren, Ron, Kuchcinski, Gregory, Langheinrich, Tobias, Lebouvier, Thibaud, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, van Minkelen, Rick, Mitchell, Sara, Moore, Katrina, Nacmias, Benedetta, Nelson, Annabel, Öijerstedt, Linn, Olives, Jaume, Ourselin, Sebastien, Padovani, Alessandro, Panman, Jessica, Papma, Janne M., Pijnenburg, Yolande, Polito, Cristina, Premi, Enrico, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rinaldi, Daisy, Rittman, Tim, Rogaeva, Ekaterina, Rollin, Adeline, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Saracino, Dario, Sayah, Sabrina, Scarpini, Elio, Schönecker, Sonja, Seelaar, Harro, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Swift, Imogen, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Tang-Wai, David, Thomas, David L., Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Todd, Emily, Van Damme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Foster, Phoebe H., Russell, Lucy L., Peakman, Georgia, Convery, Rhian S., Bouzigues, Arabella, Greaves, Caroline V., Bocchetta, Martina, Cash, David M., van Swieten, John C., Jiskoot, Lize C., Moreno, Fermin, Sanchez-Valle, Raquel, Laforce, Robert, Graff, Caroline, Masellis, Mario, Tartaglia, Carmela, Rowe, James B., Borroni, Barbara, Finger, Elizabeth, Synofzik, Matthis, Galimberti, Daniela, Vandenberghe, Rik, de Mendonça, Alexandre, Butler, Chris R., Gerhard, Alex, Ducharme, Simon, Le Ber, Isabelle, Tagliavini, Fabrizio, Santana, Isabel, Pasquier, Florence, Levin, Johannes, Danek, Adrian, Otto, Markus, Sorbi, Sandro, and Rohrer, Jonathan D.
Published: 2022
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14. Erratum to: Building bridges for innovation in ageing: Synergies between action groups of the EIP on AHA

Author: Bousquet, Jean, Bewick, M., Cano, A., Eklund, P., Fico, G., Goswami, N., Guldemond, N. A., Henderson, D., Hinkema, M. J., Liotta, G., Mair, A., Molloy, W., Monaco, A., Monsonis-Paya, I., Nizinska, A., Papadopoulos, H., Pavlickova, A., Pecorelli, S., Prados-Torres, A., Roller-Wirnsberger, R. E., Somekh, D., Vera-Muñoz, C., Visser, F., Farrell, J., Malva, J., Andersen Ranberg, K., Camuzat, T., Carriazo, A. M., Crooks, G., Gutter, Z., Iaccarino, G., de Keenoy, E. Manuel, Moda, G., Rodriguez-Mañas, L., Vontetsianos, T., Abreu, C., Alonso, J., Alonso-Bouzon, C., Ankri, J., Arredondo, M. T., Avolio, F., Bedbrook, A., Białoszewski, A. Z., Blain, H., Bourret, R., Cabrera-Umpierrez, M. F., Catala, A., O’Caoimh, R., Cesari, M., Chavannes, N. H., Correia-Da-Sousa, J., Dedeu, T., Ferrando, M., Ferri, M., Fokkens, W. J., Garcia-Lizana, F., Guérin, O., Hellings, P. W., Haahtela, T., Illario, M., Inzerilli, M. C., Lodrup Carlsen, K. C., Kardas, P., Keil, T., Maggio, M., Mendez-Zorrilla, A., Menditto, E., Mercier, J., Michel, J. P., Murray, R., Nogues, M., O’Byrne-Maguire, I., Pappa, D., Parent, A. S., Pastorino, M., Robalo-Cordeiro, C., Samolinski, B., Siciliano, P., Teixeira, A. M., Tsartara, S. I., Valiulis, A., Vandenplas, O., Vasankari, T., Vellas, B., Vollenbroek-Hutten, M., Wickman, M., Yorgancioglu, A., Zuberbier, T., Barbagallo, M., Canonica, G. W., Klimek, L., Maggi, S., Aberer, W., Akdis, C., Adcock, I. M., Agache, I., Albera, C., Alonso-Trujillo, F., Angel Guarcia, M., Annesi-Maesano, I., Apostolo, J., Arshad, S. H., Attalin, V., Avignon, A., Bachert, C., Baroni, I., Bel, E., Benson, M., Bescos, C., Blasi, F., Barbara, C., Bergmann, K. C., Bernard, P. L., Bonini, S., Bousquet, P. J., Branchini, B., Brightling, C. E., Bruguière, V., Bunu, C., Bush, A., Caimmi, D. P., Calderon, M. A., Canovas, G., Cardona, V., Carlsen, K. H., Cesario, A., Chkhartishvili, E., Chiron, R., Chivato, T., Chung, K. F., D’Angelantonio, M., de Carlo, G., Cholley, D., Chorin, F., Combe, B., Compas, B., Costa, D. J., Costa, E., Coste, O., Coupet, A. -L., Crepaldi, G., Custovic, A., Dahl, R., Dahlen, S. E., Demoly, P., Devillier, P., Didier, A., Dinh-Xuan, A. T., Djukanovic, R., Dokic, D., du Toit, G., Dubakiene, R., Dupeyron, A., Emuzyte, R., Fiocchi, A., Wagner, A., Fletcher, M., Fonseca, J., Fougère, B., Gamkrelidze, A., Garces, G., Garcia-Aymeric, J., Garcia-Zapirain, B., Gemicioğlu, B., Gouder, C., Hellquist-Dahl, B., Hermosilla-Gimeno, I., Héve, D., Holland, C., Humbert, M., Hyland, M., Johnston, S. L., Just, J., Jutel, M., Kaidashev, I. P., Kaitov, M., Kalayci, O., Kalyoncu, A. F., Keijser, W., Kerstjens, H., Knezović, J., Kowalski, M., Koppelman, G. H., Kotska, T., Kovac, M., Kull, I., Kuna, P., Kvedariene, V., Lepore, V., Macnee, W., Maggio, M., Magnan, A., Majer, I., Manning, P., Marcucci, M., Marti, T., Masoli, M., Melen, E., Miculinic, N., Mihaltan, F., Milenkovic, B., Millot-Keurinck, J., Mlinarić, H., Momas, I., Montefort, S., Morais-Almeida, M., Moreno-Casbas, T., Mösges, R., Mullol, J., Nadif, R., Nalin, M., Navarro-Pardo, E., Nekam, K., Ninot, G., Paccard, D., Pais, S., Palummeri, E., Panzner, P., Papadopoulos, N. K., Papanikolaou, C., Passalacqua, G., Pastor, E., Perrot, M., Plavec, D., Popov, T. A., Postma, D. S., Price, D., Raffort, N., Reuzeau, J. C., Robine, J. M., Rodenas, F., Robusto, F., Roche, N., Romano, A., Romano, V., Rosado-Pinto, J., Roubille, F., Ruiz, F., Ryan, D., Salcedo, T., Schmid-Grendelmeier, P., Schulz, H., Schunemann, H. J., Serrano, E., Sheikh, A., Shields, M., Siafakas, N., Scichilone, N., Siciliano, P., Skrindo, I., Smit, H. A., Sourdet, S., Sousa-Costa, E., Spranger, O., Sooronbaev, T., Sruk, V., Sterk, P. J., Todo-Bom, A., Touchon, J., Tramontano, D., Triggiani, M., Tsartara, S. I., Valero, A. L., Valovirta, E., van Ganse, E., van Hage, M., van den Berge, M., Vandenplas, O., Ventura, M. T., Vergara, I., Vezzani, G., Vidal, D., Viegi, G., Wagemann, M., Whalley, B., Wickman, M., Wilson, N., Yiallouros, P. K., Žagar, M., Zaidi, A., Zidarn, M., Hoogerwerf, E. J., Usero, J., Zuffada, R., Senn, A., and de Oliveira-Alves, B.
Published: 2023
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15. A multimodal variational autoencoder for estimating progression scores from imaging and microRNA data in rare neurodegenerative diseases.

Author: Virgilio Kmetzsch, Emmanuelle Becker, Dario Saracino, Vincent Anquetil, Daisy Rinaldi, Agnès Camuzat, Thomas Gareau, Isabelle Le Ber, and Olivier Colliot
Published: 2022
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16. Extending the phenotypic spectrum assessed by the CDR plus NACC FTLD in genetic frontotemporal dementia

Author: Samra, Kiran, Peakman, Georgia, MacDougall, Amy M., Bouzigues, Arabella, Greaves, Caroline V., Convery, Rhian S., van Swieten, John C., Jiskoot, Lize, Seelaar, Harro, Moreno, Fermin, Sanchez-Valle, Raquel, Laforce, Robert, Graff, Caroline, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B., Borroni, Barbara, Finger, Elizabeth, Synofzik, Matthis, Galimberti, Daniela, Vandenberghe, Rik, de Mendonça, Alexandre, Butler, Chris R., Gerhard, Alexander, Ducharme, Simon, Ber, Isabelle Le, Tiraboschi, Pietro, Santana, Isabel, Pasquier, Florence, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Rohrer, Jonathan D., Russell, Lucy L., Bocchetta, Martina, Cash, David, Thomas, David L., Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Fede, Giuseppe Di, Caroppo, Paola, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Papma, Janne M., Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B., Miltenberger, Gabriel, do Couto, Frederico Simões, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Samra, Kiran, Peakman, Georgia, MacDougall, Amy M., Bouzigues, Arabella, Greaves, Caroline V., Convery, Rhian S., van Swieten, John C., Jiskoot, Lize, Seelaar, Harro, Moreno, Fermin, Sanchez-Valle, Raquel, Laforce, Robert, Graff, Caroline, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B., Borroni, Barbara, Finger, Elizabeth, Synofzik, Matthis, Galimberti, Daniela, Vandenberghe, Rik, de Mendonça, Alexandre, Butler, Chris R., Gerhard, Alexander, Ducharme, Simon, Ber, Isabelle Le, Tiraboschi, Pietro, Santana, Isabel, Pasquier, Florence, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Rohrer, Jonathan D., Russell, Lucy L., Bocchetta, Martina, Cash, David, Thomas, David L., Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Fede, Giuseppe Di, Caroppo, Paola, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Papma, Janne M., Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B., Miltenberger, Gabriel, do Couto, Frederico Simões, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, and Afonso, Sónia
Abstract: INTRODUCTION: We aimed to expand the range of the frontotemporal dementia (FTD) phenotypes assessed by the Clinical Dementia Rating Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains (CDR plus NACC FTLD). METHODS: Neuropsychiatric and motor domains were added to the standard CDR plus NACC FTLD generating a new CDR plus NACC FTLD-NM scale. This was assessed in 522 mutation carriers and 310 mutation-negative controls from the Genetic Frontotemporal dementia Initiative (GENFI). RESULTS: The new scale led to higher global severity scores than the CDR plus NACC FTLD: 1.4% of participants were now considered prodromal rather than asymptomatic, while 1.3% were now considered symptomatic rather than asymptomatic or prodromal. No participants with a clinical diagnosis of an FTD spectrum disorder were classified as asymptomatic using the new scales. DISCUSSION: Adding new domains to the CDR plus NACC FTLD leads to a scale that encompasses the wider phenotypic spectrum of FTD with further work needed to validate its use more widely. Highlights: The new Clinical Dementia Rating Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains neuropsychiatric and motor (CDR plus NACC FTLD-NM) rating scale was significantly positively correlated with the original CDR plus NACC FTLD and negatively correlated with the FTD Rating Scale (FRS). No participants with a clinical diagnosis in the frontotemporal dementia spectrum were classified as asymptomatic with the new CDR plus NACC FTLD-NM rating scale. Individuals had higher global severity scores with the addition of the neuropsychiatric and motor domains. A receiver operating characteristic analysis of symptomatic diagnosis showed nominally higher areas under the curve for the new scales.
Published: 2024

17. Age at symptom onset and death and disease duration in genetic frontotemporal dementia: an international retrospective cohort study

Author: Heller, Carolin, Convery, Rhian S, Woollacott, Ione OC, Shafei, Rachelle M, Graff-Radford, Jonathan, Jones, David T, Dheel, Christina M, Savica, Rodolfo, Lapid, Maria I, Baker, Matt, Fields, Julie A, Gavrilova, Ralitza, Domoto-Reilly, Kimiko, Poos, Jackie M, Van der Ende, Emma L, Panman, Jessica L, Donker Kaat, Laura, Seelaar, Harro, Richardson, Anna, Frisoni, Giovanni, Mega, Anna, Fostinelli, Silvia, Chiang, Huei-Hsin, Alberici, Antonella, Arighi, Andrea, Fenoglio, Chiara, Heuer, Hilary, Miller, Bruce, Karydas, Anna, Fong, Jamie, João Leitão, Maria, Santiago, Beatriz, Duro, Diana, Ferreira, Carlos, Gabilondo, Alazne, De Arriba, Maria, Tainta, Mikel, Zulaica, Miren, Ferreira, Catarina, Semler, Elisa, Ludolph, Albert, Landwehrmeyer, Bernhard, Volk, Alexander E, Miltenberger, Gabriel, Verdelho, Ana, Afonso, Sónia, Tartaglia, Maria Carmela, Freedman, Morris, Rogaeva, Ekaterina, Ferrari, Camilla, Piaceri, Irene, Bessi, Valentina, Lombardi, Gemma, St-Onge, Frédéric, Doré, Marie-Claire, Bruffaerts, Rose, Vandenbulcke, Mathieu, Van den Stock, Jan, Mesulam, M Marsel, Bigio, Eileen, Koros, Christos, Papatriantafyllou, John, Kroupis, Christos, Stefanis, Leonidas, Shoesmith, Christien, Robertson, Erik, Coppola, Giovanni, Da Silva Ramos, Eliana Marisa, Geschwind, Daniel, Moore, Katrina M, Nicholas, Jennifer, Grossman, Murray, McMillan, Corey T, Irwin, David J, Massimo, Lauren, Van Deerlin, Vivianna M, Warren, Jason D, Fox, Nick C, Rossor, Martin N, Mead, Simon, Bocchetta, Martina, Boeve, Bradley F, Knopman, David S, Graff-Radford, Neill R, Forsberg, Leah K, Rademakers, Rosa, Wszolek, Zbigniew K, van Swieten, John C, Jiskoot, Lize C, Meeter, Lieke H, Dopper, Elise GP, Papma, Janne M, Snowden, Julie S, Saxon, Jennifer, Jones, Matthew, Pickering-Brown, Stuart, Le Ber, Isabelle, Camuzat, Agnès, Brice, Alexis, Caroppo, Paola, Ghidoni, Roberta, Pievani, Michela, Benussi, Luisa, Binetti, Giuliano, Dickerson, Bradford C, Lucente, Diane, Krivensky, Samantha, Graff, Caroline, Öijerstedt, Linn, Fallström, Marie, Thonberg, Håkan, Ghoshal, Nupur, Morris, John C, Borroni, Barbara, Benussi, Alberto, Padovani, Alessandro, Galimberti, Daniela, Scarpini, Elio, Fumagalli, Giorgio G, Mackenzie, Ian R, Hsiung, Ging-Yuek R, Sengdy, Pheth, Boxer, Adam L, Rosen, Howie, Taylor, Joanne B, Synofzik, Matthis, Wilke, Carlo, Sulzer, Patricia, Hodges, John R, Halliday, Glenda, Kwok, John, Sanchez-Valle, Raquel, Lladó, Albert, Borrego-Ecija, Sergi, Santana, Isabel, Almeida, Maria Rosário, Tábuas-Pereira, Miguel, Moreno, Fermin, Barandiaran, Myriam, Indakoetxea, Begoña, Levin, Johannes, Danek, Adrian, Rowe, James B, Cope, Thomas E, Otto, Markus, Anderl-Straub, Sarah, de Mendonça, Alexandre, Maruta, Carolina, Masellis, Mario, Black, Sandra E, Couratier, Philippe, Lautrette, Geraldine, Huey, Edward D, Sorbi, Sandro, Nacmias, Benedetta, Laforce, Robert, Jr, Tremblay, Marie-Pier L, Vandenberghe, Rik, Damme, Philip Van, Rogalski, Emily J, Weintraub, Sandra, Gerhard, Alexander, Onyike, Chiadi U, Ducharme, Simon, Papageorgiou, Sokratis G, Ng, Adeline Su Lyn, Brodtmann, Amy, Finger, Elizabeth, Guerreiro, Rita, Bras, Jose, and Rohrer, Jonathan D
Published: 2020
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18. Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia

Author: Bussy, A., Levy, J., Best, T., Patel, R., Cupo, L., Van Langenhove, T., Nielsen, J., Pijnenburg, Y., Waldö, M., Remes, A., Schroeter, M., Santana, I., Pasquier, F., Otto, M., Danek, A., Levin, J., Le Ber, I., Vandenberghe, R., Synofzik, M., Moreno, F., de Mendonça, A., Sanchez‐Valle, R., Laforce, R., Langheinrich, T., Gerhard, A., Graff, C., Butler, C., Sorbi, S., Jiskoot, L., Seelaar, H., van Swieten, J., Finger, E., Tartaglia, M., Masellis, M., Tiraboschi, P., Galimberti, D., Borroni, B., Rowe, J., Bocchetta, M., Rohrer, J., Devenyi, G., Chakravarty, M., Ducharme, S., Esteve, A., Nelson, A., Bouzigues, A., Heller, C., Greaves, C., Cash, D., Thomas, D., Todd, E., Benotmane, H., Zetterberg, H., Swift, I., Nicholas, J., Samra, K., Russell, L., Shafei, R., Convery, R., Timberlake, C., Cope, T., Rittman, T., Benussi, A., Premi, E., Gasparotti, R., Archetti, S., Gazzina, S., Cantoni, V., Arighi, A., Fenoglio, C., Scarpini, E., Fumagalli, G., Borracci, V., Rossi, G., Giaccone, G., Di Fede, G., Caroppo, P., Prioni, S., Redaelli, V., Tang‐Wai, D., Rogaeva, E., Castelo‐Branco, M., Freedman, M., Keren, R., Black, S., Mitchell, S., Shoesmith, C., Bartha, R., Rademakers, R., Poos, J., Papma, J., Giannini, L., van Minkelen, R., Nacmias, B., Ferrari, C., Polito, C., Lombardi, G., Bessi, V., Veldsman, M., Andersson, C., Thonberg, H., Öijerstedt, L., Jelic, V., Thompson, P., Lladó, A., Antonell, A., Olives, J., Balasa, M., Bargalló, N., Borrego‐Ecija, S., Verdelho, A., Maruta, C., Ferreira, C., Miltenberger, G., do Couto, F., Gabilondo, A., Gorostidi, A., Villanua, J., Cañada, M., Tainta, M., Zulaica, M., Barandiaran, M., Alves, P., Bender, B., Wilke, C., Graf, L., Vogels, A., Vandenbulcke, M., Van Damme, P., Bruffaerts, R., Poesen, K., Rosa‐Neto, P., Gauthier, S., Camuzat, A., Brice, A., Bertrand, A., Funkiewiez, A., Rinaldi, D., Saracino, D., Colliot, O., Sayah, S., Prix, C., Wlasich, E., Wagemann, O., Loosli, S., Schönecker, S., Hoegen, T., Lombardi, J., Anderl‐Straub, S., Rollin, A., Kuchcinski, G., Bertoux, M., Lebouvier, T., Deramecourt, V., Santiago, B., Duro, D., Leitão, M., Almeida, M., Tábuas‐Pereira, M., Afonso, S., Engel, A., Polyakova, M., Erasmus MC other, Neurology, Radiology & Nuclear Medicine, Clinical Genetics, GENetic Frontotemporal dementia Initiative (GENFI), Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B, Miltenberger, Gabriel, do Couto, Frederico Simões, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Engel, Annerose, Polyakova, Maryna, Esteve, Aitana Sogorb, Nelson, Annabel, Bouzigues, Arabella, Heller, Carolin, Greaves, Caroline V, Cash, David, Thomas, David L, Todd, Emily, Benotmane, Hanya, Zetterberg, Henrik, Swift, Imogen J, Nicholas, Jennifer, Samra, Kiran, Russell, Lucy L, Bocchetta, Martina, Shafei, Rachelle, Convery, Rhian S, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Tiraboschi, Pietro, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Papma, Janne M, Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Bussy, Aurélie [0000-0001-6695-9941], Nielsen, Jørgen E [0000-0003-0453-5582], Borroni, Barbara [0000-0001-9340-9814], Bocchetta, Martina [0000-0003-1814-5024], Devenyi, Gabriel A [0000-0002-7766-1187], Apollo - University of Cambridge Repository, and Amsterdam Neuroscience - Neurodegeneration
Subjects: C9orf72 Protein, Radiological and Ultrasound Technology, Medizin, frontotemporal dementia, Neurology, Frontotemporal Dementia, Cerebellum, Humans, magnetic resonance imaging, genetics, neuropsychiatry, Radiology, Nuclear Medicine and imaging, Human medicine, ddc:610, Neurology (clinical), Atrophy, Anatomy, genetics [Frontotemporal Dementia], genetics [C9orf72 Protein]
Abstract: Funder: Alzheimer Society of Canada; Id: http://dx.doi.org/10.13039/501100000143, Funder: Weston Brain Institute; Id: http://dx.doi.org/10.13039/100012479, Funder: Fonds de Recherche du Québec ‐ Santé, Funder: Canadian Institutes of Health Research; Id: http://dx.doi.org/10.13039/501100000024, Funder: NIHR Rare Diseases Translational Research Collaboration, Funder: Deutsche Forschungsgemeinschaft; Id: http://dx.doi.org/10.13039/501100001659, Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello-subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first-degree relatives of known symptomatic carriers. Voxel-wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic C9orf72 expansion carriers, thalamic atrophy was found compared to noncarriers, suggesting the importance of this structure in FTD prodromes. PLS analyses demonstrated that the cerebello-subcortical circuitry is related to neuropsychiatric symptoms, with significant overlap in brain/behavior patterns, but also specificity for each genetic mutation group. The largest differences were in the cerebellar atrophy (larger extent in C9orf72 expansion group) and more prominent amygdalar volume reduction in the MAPT group. Brain scores in the C9orf72 expansion carriers and MAPT carriers demonstrated covariation patterns concordant with atrophy patterns detectable up to 20 years before expected symptom onset. Overall, these results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in C9orf72 and the amygdala in MAPT carriers.
Published: 2023

19. Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018): Change management in allergic rhinitis and asthma multimorbidity using mobile technology

Author: Bousquet, J., Hellings, P.W., Aberer, W., Agache, I., Akdis, C.A., Akdis, M., Alberti, M.R., Almeida, R., Amat, F., Angles, R., Annesi-Maesano, I., Ansotegui, I.J., Anto, J.M., Arnavielle, S., Asayag, E., Asarnoj, A., Arshad, H., Avolio, F., Bacci, E., Bachert, C., Baiardini, I., Barbara, C., Barbagallo, M., Baroni, I., Barreto, B.A., Basagana, X., Bateman, E.D., Bedolla-Barajas, M., Bedbrook, A., Bewick, M., Beghé, B., Bel, E.H., Bergmann, K.C., Bennoor, K.S., Benson, M., Bertorello, L., Białoszewski, A.Z., Bieber, T., Bialek, S., Bindslev-Jensen, C., Bjermer, L., Blain, H., Blasi, F., Blua, A., Bochenska Marciniak, M., Bogus-Buczynska, I., Boner, A.L., Bonini, M., Bonini, S., Bosnic-Anticevich, C.S., Bosse, I., Bouchard, J., Boulet, L.P., Bourret, R., Bousquet, P.J., Braido, F., Briedis, V., Brightling, C.E., Brozek, J., Bucca, C., Buhl, R., Buonaiuto, R., Panaitescu, C., Burguete Cabañas, M.T., Burte, E., Bush, A., Caballero-Fonseca, F., Caillot, D., Caimmi, D., Calderon, M.A., Camargos, P.A.M., Camuzat, T., Canfora, G., Canonica, G.W., Cardona, V., Carlsen, K.H., Carreiro-Martins, P., Carriazo, A.M., Carr, W., Cartier, C., Casale, T., Castellano, G., Cecchi, L., Cepeda Sarabia, A.M., Chavannes, N.H., Chen, Y., Chiron, R., Chivato, T., Chkhartishvili, E., Chuchalin, A.G., Chung, K.F., Ciaravolo, M.M., Ciceran, A., Cingi, C., Ciprandi, G., Carvalho Coehlo, A.C., Colas, L., Colgan, E., Coll, J., Conforti, D., Correia de Sousa, J., Cortés-Grimaldo, R.M., Corti, F., Costa, E., Costa-Dominguez, M.C., Courbis, A.L., Cox, L., Crescenzo, M., Cruz, A.A., Custovic, A., Czarlewski, W., Dahlen, S.E., Dario, C., da Silva, J., Dauvilliers, Y., Darsow, U., De Blay, F., De Carlo, G., Dedeu, T., de Fátima Emerson, M., De Feo, G., De Vries, G., De Martino, B., de Paula Motta Rubini, N., Deleanu, D., Demoly, P., Denburg, J.A., Devillier, P., Di Capua Ercolano, S., Di Carluccio, N., Didier, A., Dokic, D., Dominguez-Silva, M.G., Douagui, H., Dray, G., Dubakiene, R., Durham, S.R., Du Toit, G., Dykewicz, M.S., El-Gamal, Y., Eklund, P., Eller, E., Emuzyte, R., Farrell, J., Farsi, A., Ferreira de Mello, J., Jr., Ferrero, J., Fink-Wagner, A., Fiocchi, A., Fokkens, W.J., Fonseca, J.A., Fontaine, J.F., Forti, S., Fuentes-Perez, J.M., Gálvez-Romero, J.L., Gamkrelidze, A., Garcia-Aymerich, J., García-Cobas, C.Y., Garcia-Cruz, M.H., Gemicioğlu, B., Genova, S., George, C., Gereda, J.E., Gerth van Wijk, R., Gomez, R.M., Gómez-Vera, J., González Diaz, S., Gotua, M., Grisle, I., Guidacci, M., Guldemond, N.A., Gutter, Z., Guzmán, M.A., Haahtela, T., Hajjam, J., Hernández, L., Hourihane, J.O.'B., Huerta-Villalobos, Y.R., Humbert, M., Iaccarino, G., Illario, M., Ivancevich, J.C., Jares, E.J., Jassem, E., Johnston, S.L., Joos, G., Jung, K.S., Jutel, M., Kaidashev, I., Kalayci, O., Kalyoncu, A.F., Karjalainen, J., Kardas, P., Keil, T., Keith, P.K., Khaitov, M., Khaltaev, N., Kleine-Tebbe, J., Klimek, L., Kowalski, M.L., Kuitunen, M., Kull, I., Kuna, P., Kupczyk, M., Kvedariene, V., Krzych-Fałta, E., Lacwik, P., Larenas-Linnemann, D., Laune, D., Lauri, D., Lavrut, J., Le, L.T.T., Lessa, M., Levato, G., Li, J., Lieberman, P., Lipiec, A., Lipworth, B., Lodrup Carlsen, K.C., Louis, R., Lourenço, O., Luna-Pech, J.A., Maciej, K., Magnan, A., Mahboub, B., Maier, D., Mair, A., Majer, I., Malva, J., Mandajieva, E., Manning, P., De Manuel Keenoy, E., Marshall, G.D., Masjedi, M.R., Maspero, J.F., Mathieu-Dupas, E., Matta Campos, J.J., Matos, A.L., Maurer, M., Mavale-Manuel, S., Mayora, O., Medina-Avalos, M.A., Melén, E., Melo-Gomes, E., Meltzer, E.O., Menditto, E., Mercier, J., Miculinic, N., Mihaltan, F., Milenkovic, B., Moda, G., Mogica-Martinez, M.D., Mohammad, Y., Momas, I., Montefort, S., Monti, R., Mora Bogado, D., Morais-Almeida, M., Morato-Castro, F.F., Mösges, R., Mota-Pinto, A., Moura Santo, P., Mullol, J., Münter, L., Muraro, A., Murray, R., Naclerio, R., Nadif, R., Nalin, M., Napoli, L., Namazova-Baranova, L., Neffen, H., Niedeberger, V., Nekam, K., Neou, A., Nieto, A., Nogueira-Silva, L., Nogues, M., Novellino, E., Nyembue, T.D., O'Hehir, R.E., Odzhakova, C., Ohta, K., Okamoto, Y., Okubo, K., Onorato, G.L., Ortega Cisneros, M., Ouedraogo, S., Pali-Schöll, I., Palkonen, S., Panzner, P., Papadopoulos, N.G., Park, H.S., Papi, A., Passalacqua, G., Paulino, E., Pawankar, R., Pedersen, S., Pépin, J.L., Pereira, A.M., Persico, M., Pfaar, O., Phillips, J., Picard, R., Pigearias, B., Pin, I., Pitsios, C., Plavec, D., Pohl, W., Popov, T.A., Portejoie, F., Potter, P., Pozzi, A.C., Price, D., Prokopakis, E.P., Puy, R., Pugin, B., Pulido Ross, R.E., Przemecka, M., Rabe, K.F., Raciborski, F., Rajabian-Soderlund, R., Reitsma, S., Ribeirinho, I., Rimmer, J., Rivero-Yeverino, D., Rizzo, J.A., Rizzo, M.C., Robalo-Cordeiro, C., Rodenas, F., Rodo, X., Rodriguez Gonzalez, M., Rodriguez-Mañas, L., Rolland, C., Rodrigues Valle, S., Roman Rodriguez, M., Romano, A., Rodriguez-Zagal, E., Rolla, G., Roller-Wirnsberger, R.E., Romano, M., Rosado-Pinto, J., Rosario, N., Rottem, M., Ryan, D., Sagara, H., Salimäki, J., Samolinski, B., Sanchez-Borges, M., Sastre-Dominguez, J., Scadding, G.K., Schunemann, H.J., Scichilone, N., Schmid-Grendelmeier, P., Serpa, F.S., Shamai, S., Sheikh, A., Sierra, M., Simons, F.E.R., Siroux, V., Sisul, J.C., Skrindo, I., Solé, D., Somekh, D., Sondermann, M., Sooronbaev, T., Sova, M., Sorensen, M., Sorlini, M., Spranger, O., Stellato, C., Stelmach, R., Stukas, R., Sunyer, J., Strozek, J., Szylling, A., Tebyriçá, J.N., Thibaudon, M., To, T., Todo-Bom, A., Tomazic, P.V., Toppila-Salmi, S., Trama, U., Triggiani, M., Suppli Ulrik, C., Urrutia-Pereira, M., Valenta, R., Valero, A., Valiulis, A., Valovirta, E., van Eerd, M., van Ganse, E., van Hague, M., Vandenplas, O., Ventura, M.T., Vezzani, G., Vasankari, T., Vatrella, A., Verissimo, M.T., Viart, F., Viegi, M., Vicheva, D., Vontetsianos, T., Wagenmann, M., Walker, S., Wallace, D., Wang, D.Y., Waserman, S., Werfel, T., Westman, M., Wickman, M., Williams, D.M., Williams, S., Wilson, N., Wright, J., Wroczynski, P., Yakovliev, P., Yawn, B.P., Yiallouros, P.K., Yorgancioglu, A., Yusuf, O.M., Zar, H.J., Zhang, L., Zhong, N., Zernotti, M.E., Zidarn, M., Zuberbier, T., Zubrinich, C., Zurkuhlen, A., Bousquet, Jean, Hellings, Peter W., Agache, Ioana, Amat, Flore, Annesi-Maesano, Isabella, Ansotegui, Ignacio J., Anto, Josep M., Bachert, Claus, Bateman, Eric D., Bedbrook, Anna, Bennoor, Kazi, Bewick, Mickael, Bindslev-Jensen, Carsten, Bosnic-Anticevich, Sinthia, Bosse, Isabelle, Brozek, Jan, Brussino, Luisa, Canonica, Giorgio W., Cardona, Victoria, Casale, Thomas, Cepeda Sarabia, Alfonso M., Chavannes, Niels H., Cecchi, Lorenzo, Correia de Sousa, Jaime, Costa, Elisio, Cruz, Alvaro A., Czarlewski, Wienczyslawa, De Carlo, Giuseppe, De Feo, Giulia, Demoly, Pascal, Devillier, Philippe, Dykewicz, Mark S., El-Gamal, Yehia, Eller, Esben E., Fonseca, Joao A., Fontaine, Jean-François, Fokkens, Wytske J., Guzmán, Maria-Antonieta, Haahtela, Tari, Illario, Maddalena, Ivancevich, Juan-Carlos, Just, Jocelyne, Kaidashev, Igor, Khaitov, Musa, Kalayci, Omer, Keil, Thomas, Klimek, Ludger, Kowalski, Marek L., Kuna, Piotr, Kvedariene, Violeta, Larenas-Linnemann, Desiree, Laune, Daniel, Le, Lan T.T., Carlsen, Karin Lodrup, Lourenço, Olga, Mahboub, Bassam, Mair, Alpana, Menditto, Enrica, Milenkovic, Branislava, Morais-Almeida, Mario, Mösges, Ralph, Mullol, Joaquim, Murray, Ruth, Naclerio, Robert, Namazova-Baranova, Leyla, Novellino, Ettore, O'Hehir, Robyn E., Ohta, Ken, Okamoto, Yoshitaka, Okubo, Kimi, Onorato, Gabrielle L., Palkonen, Susanna, Panzner, Petr, Papadopoulos, Nikos G., Park, Hae-Sim, Paulino, Ema, Pawankar, Ruby, Pfaar, Oliver, Plavec, Davor, Popov, Ted A., Potter, Paul, Prokopakis, Emmanuel P., Rottem, Menachem, Ryan, Dermot, Salimäki, Johanna, Samolinski, Boleslaw, Sanchez-Borges, Mario, Schunemann, Holger J., Sheikh, Aziz, Sisul, Juan-Carlos, Rajabian-Söderlund, Rojin, Sooronbaev, Talant, Stellato, Cristiana, To, Teresa, Todo-Bom, Ana-Maria, Tomazic, Peter-Valentin, Toppila-Salmi, Sanna, Valero, Antonio, Valiulis, Arunas, Valovirta, Erkka, Ventura, Maria-Teresa, Wagenmann, Martin, Wang, De Yun, Wallace, Dana, Waserman, Susan, Wickman, Magnus, Yorgancioglu, Arzu, Zhang, Luo, Zhong, Nanshan, Zidarn, Mihaela, and Zuberbier, Torsten
Published: 2019
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20. Loss of brainstem white matter predicts onset and motor neuron symptoms in C9orf72 expansion carriers: a GENFI study

Author: Pérez-Millan, Agnès, Borrego-Écija, Sergi, van Swieten, John C., Jiskoot, Lize, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B., Borroni, Barbara, Finger, Elizabeth, Synofzik, Matthis, Galimberti, Daniela, Vandenberghe, Rik, de Mendonça, Alexandre, Butler, Chris R., Gerhard, Alexander, Ducharme, Simon, Le Ber, Isabelle, Santana, Isabel, Pasquier, Florence, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Tiraboschi, Pietro, Seelaar, Harro, Langheinrich, Tobias, Rohrer, Jonathan D., Sala-Llonch, Roser, Sánchez-Valle, Raquel, GENFI The Genetic FTD Initiative, Ullgren, Abbe, Rollin, Adeline, Camuzat, Agnès, Esteve, Aitana Sogorb, Gabilondo, Alazne, Lladó, Albert, Benussi, Alberto, Brice, Alexis, Gorostidi, Ana, Verdelho, Ana, Arighi, Andrea, Antonell, Anna, Bertrand, Anne, Engel, Annerose, Vogels, Annick, Bouzigues, Arabella, Funkiewiez, Aurélie, Nacmias, Benedetta, Bender, Benjamin, Ferrari, Camilla, Wilke, Carlo, Heller, Carolin, Maruta, Carolina, Greaves, Caroline V., Timberlake, Carolyn, Ferreira, Catarina B., Prix, Catharina, Fenoglio, Chiara, Shoesmith, Christen, Polito, Cristina, Rinaldi, Daisy, Saracino, Dario, Cash, David, Thomas, David L., Tang-Wai, David, Duro, Diana, Rogaeva, Ekaterina, Scarpini, Elio, Wlasich, Elisabeth, Buratti, Emanuele, Todd, Emily, Premi, Enrico, do Couto, Frederico Simões, Miltenberger, Gabriel, Lombardi, Gemma, Rossi, Giacomina, Fumagalli, Giorgio, Giaccone, Giorgio, Di Fede, Giuseppe, Kuchcinski, Gregory, Benotmane, Hanya, Zetterberg, Henrik, Swift, Imogen J., Poos, Jackie, M. Papma, Janne, Nicholas, Jennifer, Durães, João, Lombardi, Jolina, Juncà-Parella, Jordi, Sarto, Jordi, Villanua, Jorge, Samra, Kiran, Poesen, Koen, Öijerstedt, Linn, Graf, Lisa, Giannini, Lucia, Russell, Lucy L., Leitão, Maria João, Almeida, Maria Rosario, Serpente, Maria, Lima, Marisa, Cañada, Marta, Bocchetta, Martina, Polyakova, Maryna, Vandenbulcke, Mathieu, Bertoux, Maxime, Veldsman, Michele, Castelo-Branco, Miguel, Tábuas-Pereira, Miguel, Tainta, Mikel, Balasa, Mircea, Zulaica, Miren, Freedman, Morris, Barandiaran, Myriam, Bargalló, Nuria, Wagemann, Olivia, Colliot, Olivier, Caroppo, Paola, Alves, Patricia, Thompson, Paul, Rosa-Neto, Pedro, Van Damme, Philip, Shafei, Rachelle, Convery, Rhian S., van Minkelen, Rick, Bartha, Robart, Gasparotti, Roberto, Keren, Ron, Rademakers, Rosa, Bruffaerts, Rose, Sayah, Sabrina, Black, Sandra, Loosli, Sandra, Mitchell, Sara, Prioni, Sara, Anderl-Straub, Sarah, Gauthier, Serge, Afonso, Sónia, Schönecker, Sonja, Gazzina, Stefano, Lebouvier, Thibaud, Cope, Thomas, Rittman, Timothy, Hoegen, Tobias, Bessi, Valentina, Cantoni, Valentina, Redaelli, Veronica, Jelic, Vesna, Deramecourt, Vincent, Borracci, Vittoria, The Genetic FTD Initiative, GENFI, Almeida, Maria Rosario, Serpente, Maria, Lima, Marisa, Cañada, Marta, Bocchetta, Martina, Polyakova, Maryna, Vandenbulcke, Mathieu, Bertoux, Maxime, Veldsman, Michele, Castelo-Branco, Miguel, Tábuas-Pereira, Miguel, Tainta, Mikel, Balasa, Mircea, Zulaica, Miren, Freedman, Morris, Barandiaran, Myriam, Bargalló, Nuria, Wagemann, Olivia, Colliot, Olivier, Caroppo, Paola, Alves, Patricia, Thompson, Paul, Rosa-Neto, Pedro, Van Damme, Philip, Tiraboschi, Pietro, Shafei, Rachelle, Convery, Rhian S, van Minkelen, Rick, Bartha, Robart, Gasparotti, Roberto, Keren, Ron, Rademakers, Rosa, Bruffaerts, Rose, Sayah, Sabrina, Black, Sandra, Loosli, Sandra, Mitchell, Sara, Prioni, Sara, Anderl-Straub, Sarah, Gauthier, Serge, Afonso, Sónia, Schönecker, Sonja, Gazzina, Stefano, Lebouvier, Thibaud, Cope, Thomas, Rittman, Timothy, Hoegen, Tobias, Bessi, Valentina, Cantoni, Valentina, Redaelli, Veronica, Jelic, Vesna, Deramecourt, Vincent, Borracci, Vittoria, Ullgren, Abbe, Rollin, Adeline, Camuzat, Agnès, Esteve, Aitana Sogorb, Gabilondo, Alazne, Lladó, Albert, Benussi, Alberto, Brice, Alexis, Gorostidi, Ana, Verdelho, Ana, Arighi, Andrea, Antonell, Anna, Bertrand, Anne, Engel, Annerose, Vogels, Annick, Bouzigues, Arabella, Funkiewiez, Aurélie, Nacmias, Benedetta, Bender, Benjamin, Ferrari, Camilla, Wilke, Carlo, Heller, Carolin, Maruta, Carolina, Greaves, Caroline V, Timberlake, Carolyn, Ferreira, Catarina B, Prix, Catharina, Fenoglio, Chiara, Shoesmith, Christen, Polito, Cristina, Rinaldi, Daisy, Saracino, Dario, Cash, David, Thomas, David L, Tang-Wai, David, Duro, Diana, Rogaeva, Ekaterina, Scarpini, Elio, Wlasich, Elisabeth, Buratti, Emanuele, Todd, Emily, Premi, Enrico, do Couto, Frederico Simões, Miltenberger, Gabriel, Lombardi, Gemma, Rossi, Giacomina, Fumagalli, Giorgio, Giaccone, Giorgio, Di Fede, Giuseppe, Kuchcinski, Gregory, Benotmane, Hanya, Zetterberg, Henrik, Swift, Imogen J, Poos, Jackie, M Papma, Janne, Nicholas, Jennifer, Durães, João, Lombardi, Jolina, Juncà-Parella, Jordi, Sarto, Jordi, Villanua, Jorge, Samra, Kiran, Poesen, Koen, Öijerstedt, Linn, Graf, Lisa, Giannini, Lucia, Russell, Lucy L, and Leitão, Maria João
Subjects: diagnostic imaging [Brain Stem], pathology [Motor Neurons], diagnostic imaging [Motor Neuron Disease], diagnostic imaging [Frontotemporal Dementia], diagnostic imaging [White Matter], pathology [Brain Stem], Neurology, pathology [White Matter], pathology [Frontotemporal Dementia], Mutation, C9orf72, Humans, genetics [Motor Neuron Disease], ddc:610, Human medicine, Neurology (clinical), genetics [Frontotemporal Dementia], genetics [C9orf72 Protein], Brainstem, GENFI, Frontotemporal dementia
Abstract: Background and objectives The C9orf72 expansion is the most common genetic cause of frontotemporal dementia (FTD) and/or motor neuron disease (MND). Corticospinal degeneration has been described in post-mortem neuropathological studies in these patients, especially in those with MND. We used MRI to analyze white matter (WM) volumes in presymptomatic and symptomatic C9orf72 expansion carriers and investigated whether its measure may be helpful in predicting the onset of symptoms. Methods We studied 102 presymptomatic C9orf72 mutation carriers, 52 symptomatic carriers: 42 suffering from FTD and 11 from MND, and 75 non-carriers from the Genetic Frontotemporal dementia Initiative (GENFI). All subjects underwent T1-MRI acquisition. We used FreeSurfer to estimate the volume proportion of WM in the brainstem regions (midbrain, pons, and medulla oblongata). We calculated group differences with ANOVA tests and performed linear and non-linear regressions to assess group-by-age interactions. Results A reduced WM ratio was found in all brainstem subregions in symptomatic carriers compared to both noncarriers and pre-symptomatic carriers. Within symptomatic carriers, MND patients presented a lower ratio in pons and medulla oblongata compared with FTD patients. No differences were found between presymptomatic carriers and non-carriers. Clinical severity was negatively associated with the WM ratio. C9orf72 carriers presented greater age-related WM loss than non-carriers, with MND patients showing significantly more atrophy in pons and medulla oblongata. Discussion We find consistent brainstem WM loss in C9orf72 symptomatic carriers with differences related to the clinical phenotype supporting the use of brainstem measures as neuroimaging biomarkers for disease tracking.
Published: 2022

21. Motor symptoms in genetic frontotemporal dementia: developing a new module for clinical rating scales

Author: Samra, K, MacDougall, AM, Peakman, G, Bouzigues, A, Bocchetta, M, Cash, DM, Greaves, CV, Convery, RS, van Swieten, JC, Jiskoot, L, Seelaar, H, Butler, CR, Fenoglio, C, Rohrer, JD, Gerhard, A, Ducharme, S, Le Ber, I, Tiraboschi, P, Santana, I, Pasquier, F, Levin, J, Shoesmith, C, Otto, M, Russell, LL, Nelson, A, Cash, D, Thomas, DL, Todd, E, Ferrari, C, Benotmane, H, Timberlake, C, Gabilondo, A, Cope, T, Rittman, T, Benussi, A, Premi, E, Gasparotti, R, Thompson, P, Archetti, S, Fumagalli, G, do Couto, FS, Borracci, V, Polito, C, Rossi, G, Giaccone, G, Di Fede, G, Caroppo, P, Ferreira, CB, Prioni, S, Langheinrich, T, Redaelli, V, Lladó, A, Bartha, R, Tang-Wai, D, Rogaeva, E, Castelo-Branco, M, Freedman, M, Keren, R, Black, S, Mitchell, S, Miltenberger, G, Rademakers, R, Poos, J, Papma, JM, Giannini, L, van Minkelen, R, Pijnenburg, Y, Gauthier, S, Nacmias, B, Lombardi, G, Bessi, V, Veldsman, M, Andersson, C, Thonberg, H, Öijerstedt, L, Prix, C, Jelic, V, Antonell, A, Graff, C, Olives, J, Balasa, M, Bargalló, N, Borrego-Ecija, S, Verdelho, A, Kuchcinski, G, Maruta, C, Gorostidi, A, Laforce, R, Villanua, J, Wlasich, E, Cañada, M, Tainta, M, Zulaica, M, Barandiaran, M, Moreno, F, Alves, P, Bender, B, Bertoux, M, Wilke, C, Lebouvier, T, Camuzat, A, Graf, L, Vogels, A, Vandenbulcke, M, Van Damme, P, Bruffaerts, R, Poesen, K, Rosa-Neto, P, Sanchez-Valle, R, Brice, A, Bertrand, A, Funkiewiez, A, Rinaldi, D, Saracino, D, Colliot, O, Sorbi, S, Sayah, S, Wagemann, O, Loosli, S, Schönecker, S, Hoegen, T, Lombardi, J, Anderl-Straub, S, Nicholas, J, Rollin, A, Deramecourt, V, Arighi, A, Santiago, B, Duro, D, Leitão, MJ, Almeida, MR, Tábuas-Pereira, M, Gazzina, S, Afonso, S, Masellis, M, Tartaglia, C, Shafei, R, Rowe, JB, Borroni, B, Finger, E, Synofzik, M, Galimberti, D, Vandenberghe, R, de Mendonça, A, Cantoni, V, Genetic FTD Initiative (GENFI), Samra, Kiran [0000-0002-3105-7099], Apollo - University of Cambridge Repository, Maruta, Carolina, Ferreira, Catarina B, Miltenberger, Gabriel, do Couto, Frederico Simões, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Nelson, Annabel, Bocchetta, Martina, Cash, David, Thomas, David L, Todd, Emily, Benotmane, Hanya, Nicholas, Jennifer, Samra, Kiran, Shafei, Rachelle, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Tiraboschi, Pietro, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Papma, Janne M, Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, and Verdelho, Ana
Subjects: Progranulin, Clinical Neurology, C9ORF72, tau Proteins, AMYOTROPHIC-LATERAL-SCLEROSIS, diagnosis [Frontotemporal Dementia], C9orf72, Tremor, Genetics, Humans, ddc:610, genetics [Frontotemporal Dementia], genetics [C9orf72 Protein], MUTATION, Science & Technology, C9orf72 Protein, HERITABILITY, Amyotrophic Lateral Sclerosis, PROGRESSIVE SUPRANUCLEAR PALSY, COGNITIVE IMPAIRMENT, REPEAT EXPANSION, genetics [tau Proteins], Motor, PATHOLOGICAL FEATURES, Neurology, FOS: Biological sciences, Frontotemporal Dementia, Mutation, Human medicine, Neurosciences & Neurology, Neurology (clinical), Tau, TAU, Life Sciences & Biomedicine, Frontotemporal dementia, PARKINSONISM
Abstract: Funder: CIBERNED, Funder: Canadian Institutes of Health Research; doi: http://dx.doi.org/10.13039/501100000024, Funder: Lemaire Family Foundation, Funder: Swedish Frontotemporal Dementia Initiative, Funder: Italian Ministry of Health, Funder: Weston Brain Institute; doi: http://dx.doi.org/10.13039/100012479, Funder: Mady Browaaeys Fund, Funder: Miriam Marks Brain Research UK, Funder: Bluefield Project, OBJECTIVE: To investigate the optimal method of adding motor features to a clinical rating scale for frontotemporal dementia (FTD). METHODS: Eight hundred and thirty-two participants from the international multicentre Genetic FTD Initiative (GENFI) study were recruited: 522 mutation carriers (with C9orf72, GRN and MAPT mutations) and 310 mutation-negative controls. A standardised clinical questionnaire was used to assess eight motor symptoms (dysarthria, dysphagia, tremor, slowness, weakness, gait disorder, falls and functional difficulties using hands). Frequency and severity of each motor symptom was assessed, and a principal component analysis (PCA) was performed to identify how the different motor symptoms loaded together. Finally, addition of a motor component to the CDR® plus NACC FTLD was investigated (CDR® plus NACC FTLD-M). RESULTS: 24.3% of mutation carriers had motor symptoms (31.7% C9orf72, 18.8% GRN, 19.3% MAPT) compared to 6.8% of controls. Slowness and gait disorder were the commonest in all genetic groups while tremor and falls were the least frequent. Symptom severity scores were similar to equivalent physical motor examination scores. PCA revealed that all motor symptoms loaded together so a single additional motor component was added to the CDR® plus NACC FTLD to form the CDR® plus NACC FTLD-M. Individual global scores were more severe with the CDR® plus NACC FTLD-M, and no patients with a clinically diagnosed motor disorder (ALS/FTD-ALS or parkinsonism) were classified anymore as asymptomatic (unlike the CDR® plus NACC FTLD alone). CONCLUSIONS: Motor features are present in mutation carriers at all disease stages across all three genetic groups. Inclusion of motor symptoms in a rating scale that can be used in future clinical trials will not only ensure a more accurate severity measure is recorded but that a wider spectrum of FTD phenotypes can be included in the same trial.
Published: 2022

22. Differential early subcortical involvement in genetic FTD within the GENFI cohort

Author: Martina Bocchetta, Emily G. Todd, Georgia Peakman, David M. Cash, Rhian S. Convery, Lucy L. Russell, David L. Thomas, Juan Eugenio Iglesias, John C. van Swieten, Lize C. Jiskoot, Harro Seelaar, Barbara Borroni, Daniela Galimberti, Raquel Sanchez-Valle, Robert Laforce, Fermin Moreno, Matthis Synofzik, Caroline Graff, Mario Masellis, Maria Carmela Tartaglia, James B. Rowe, Rik Vandenberghe, Elizabeth Finger, Fabrizio Tagliavini, Alexandre de Mendonça, Isabel Santana, Chris R. Butler, Simon Ducharme, Alexander Gerhard, Adrian Danek, Johannes Levin, Markus Otto, Sandro Sorbi, Isabelle Le Ber, Florence Pasquier, Jonathan D. Rohrer, Sónia Afonso, Maria Rosario Almeida, Sarah Anderl-Straub, Christin Andersson, Anna Antonell, Silvana Archetti, Andrea Arighi, Mircea Balasa, Myriam Barandiaran, Nuria Bargalló, Robart Bartha, Benjamin Bender, Alberto Benussi, Maxime Bertoux, Anne Bertrand, Valentina Bessi, Sandra Black, Sergi Borrego-Ecija, Jose Bras, Alexis Brice, Rose Bruffaerts, Agnès Camuzat, Marta Cañada, Valentina Cantoni, Paola Caroppo, Miguel Castelo-Branco, Olivier Colliot, Thomas Cope, Vincent Deramecourt, María de Arriba, Giuseppe Di Fede, Alina Díez, Diana Duro, Chiara Fenoglio, Camilla Ferrari, Catarina B. Ferreira, Nick Fox, Morris Freedman, Giorgio Fumagalli, Aurélie Funkiewiez, Alazne Gabilondo, Roberto Gasparotti, Serge Gauthier, Stefano Gazzina, Giorgio Giaccone, Ana Gorostidi, Caroline Greaves, Rita Guerreiro, Carolin Heller, Tobias Hoegen, Begoña Indakoetxea, Vesna Jelic, Hans-Otto Karnath, Ron Keren, Gregory Kuchcinski, Tobias Langheinrich, Thibaud Lebouvier, Maria João Leitão, Albert Lladó, Gemma Lombardi, Sandra Loosli, Carolina Maruta, Simon Mead, Lieke Meeter, Gabriel Miltenberger, Rick van Minkelen, Sara Mitchell, Katrina Moore, Benedetta Nacmias, Annabel Nelson, Jennifer Nicholas, Linn Öijerstedt, Jaume Olives, Sebastien Ourselin, Alessandro Padovani, Jessica Panman, Janne M. Papma, Yolande Pijnenburg, Cristina Polito, Enrico Premi, Sara Prioni, Catharina Prix, Rosa Rademakers, Veronica Redaelli, Daisy Rinaldi, Tim Rittman, Ekaterina Rogaeva, Adeline Rollin, Pedro Rosa-Neto, Giacomina Rossi, Martin Rossor, Beatriz Santiago, Dario Saracino, Sabrina Sayah, Elio Scarpini, Sonja Schönecker, Elisa Semler, Rachelle Shafei, Christen Shoesmith, Imogen Swift, Miguel Tábuas-Pereira, Mikel Tainta, Ricardo Taipa, David Tang-Wai, Paul Thompson, Hakan Thonberg, Carolyn Timberlake, Pietro Tiraboschi, Philip Van Damme, Mathieu Vandenbulcke, Michele Veldsman, Ana Verdelho, Jorge Villanua, Jason Warren, Carlo Wilke, Ione Woollacott, Elisabeth Wlasich, Henrik Zetterberg, and Miren Zulaica
Subjects: Genetic frontotemporal dementia, MRI imaging, Brain volumetry, Presymptomatic stage, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract: Background: Studies have previously shown evidence for presymptomatic cortical atrophy in genetic FTD. Whilst initial investigations have also identified early deep grey matter volume loss, little is known about the extent of subcortical involvement, particularly within subregions, and how this differs between genetic groups. Methods: 480 mutation carriers from the Genetic FTD Initiative (GENFI) were included (198 GRN, 202 C9orf72, 80 MAPT), together with 298 non-carrier cognitively normal controls. Cortical and subcortical volumes of interest were generated using automated parcellation methods on volumetric 3 T T1-weighted MRI scans. Mutation carriers were divided into three disease stages based on their global CDR® plus NACC FTLD score: asymptomatic (0), possibly or mildly symptomatic (0.5) and fully symptomatic (1 or more). Results: In all three groups, subcortical involvement was seen at the CDR 0.5 stage prior to phenoconversion, whereas in the C9orf72 and MAPT mutation carriers there was also involvement at the CDR 0 stage. In the C9orf72 expansion carriers the earliest volume changes were in thalamic subnuclei (particularly pulvinar and lateral geniculate, 9–10%) cerebellum (lobules VIIa-Crus II and VIIIb, 2–3%), hippocampus (particularly presubiculum and CA1, 2–3%), amygdala (all subregions, 2–6%) and hypothalamus (superior tuberal region, 1%). In MAPT mutation carriers changes were seen at CDR 0 in the hippocampus (subiculum, presubiculum and tail, 3–4%) and amygdala (accessory basal and superficial nuclei, 2–4%). GRN mutation carriers showed subcortical differences at CDR 0.5 in the presubiculum of the hippocampus (8%). Conclusions: C9orf72 expansion carriers show the earliest and most widespread changes including the thalamus, basal ganglia and medial temporal lobe. By investigating individual subregions, changes can also be seen at CDR 0 in MAPT mutation carriers within the limbic system. Our results suggest that subcortical brain volumes may be used as markers of neurodegeneration even prior to the onset of prodromal symptoms.
Published: 2021
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23. Disease Progression Score Estimation From Multimodal Imaging and MicroRNA Data Using Supervised Variational Autoencoders

Author: Virgilio Kmetzsch, Emmanuelle Becker, Dario Saracino, Daisy Rinaldi, Agnes Camuzat, Isabelle Le Ber, Olivier Colliot, Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Dynamics, Logics and Inference for biological Systems and Sequences (Dyliss), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-GESTION DES DONNÉES ET DE LA CONNAISSANCE (IRISA-D7), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), The research leading to these results has received funding from the French government under management of Agence Nationale de la Recherche, references ANR-19-P3IA-0001 (PRAIRIE 3IA Institute), ANR-10-IAIHU-06, project PREV-DEMALS (grant number ANR-14-CE15-0016-07), and from the Inria Project Lab Program (project Neuromarkers)., ANR-19-P3IA-0001,PRAIRIE,PaRis Artificial Intelligence Research InstitutE(2019), ANR-14-CE15-0016,PREV-DEMALS,Prédire pour prévenir les démences frontotemporales (DFT) et la sclérose latérale amyotrophique (SLA)(2014), Colliot, Olivier, PaRis Artificial Intelligence Research InstitutE - - PRAIRIE2019 - ANR-19-P3IA-0001 - P3IA - VALID, and Appel à projets générique - Prédire pour prévenir les démences frontotemporales (DFT) et la sclérose latérale amyotrophique (SLA) - - PREV-DEMALS2014 - ANR-14-CE15-0016 - Appel à projets générique - VALID
Subjects: [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], Deep learning, MicroRNA, Neuroimaging, Health Informatics, Variational autoencoder, Neurodegenerative disease, Disease progression score, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], Computer Science Applications, [INFO.INFO-CV] Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Multimodal data, [INFO.INFO-TI] Computer Science [cs]/Image Processing [eess.IV], Health Information Management, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Electrical and Electronic Engineering, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, [SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing
Abstract: International audience; Frontotemporal dementia and amyotrophic lateral sclerosis are rare neurodegenerative diseases with no effective treatment. The development of biomarkers allowing an accurate assessment of disease progression is crucial for evaluating new therapies. Concretely, neuroimaging and transcriptomic (microRNA) data have been shown useful in tracking their progression. However, no single biomarker can accurately measure progression in these complex diseases. Additionally, large samples are not available for such rare disorders. It is thus essential to develop methods that can model disease progression by combining multiple biomarkers from small samples. In this paper, we propose a new framework for computing a disease progression score (DPS) from cross-sectional multimodal data. Specifically, we introduce a supervised multimodal variational autoencoder that can infer a meaningful latent space, where latent representations are placed along a disease trajectory. A score is computed by orthogonal projections onto this path. We evaluate our framework with multiple synthetic datasets and with a real dataset containing 14 patients, 40 presymptomatic genetic mutation carriers and 37 controls from the PREV-DEMALS study. There is no ground truth for the DPS in real-world scenarios, therefore we use the area under the ROC curve (AUC) as a proxy metric. Results with the synthetic datasets support this choice, since the higher the AUC, the more accurate the predicted simulated DPS. Experiments with the real dataset demonstrate better performance in comparison with stateof-the-art approaches. The proposed framework thus leverages cross-sectional multimodal datasets with small sample sizes to objectively measure disease progression, with potential application in clinical trials.
Published: 2022

24. Early neurotransmitters changes in prodromal frontotemporal dementia

Author: Premi, Enrico, Pengo, Marta, Mattioli, Irene, Cantoni, Valentina, Dukart, Juergen, Gasparotti, Roberto, Buratti, Emanuele, Padovani, Alessandro, Bocchetta, Martina, Todd, Emily G., Bouzigues, Arabella, Cash, David M., Convery, Rhian S., Russell, Lucy L., Thomas, David L., van Swieten, John C., Jiskoot, Lize C., Seelaar, Harro, Galimberti, Daniela, Sanchez-Valle, Raquel, Laforce, Robert, Moreno, Fermin, Synofzik, Matthis, Graff, Caroline, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B., Tsvetanov, Kamen A., Vandenberghe, Rik, Finger, Elizabeth, Tagliavini, Fabrizio, de Mendonça, Alexandre, Santana, Isabel, Butler, Chris R., Ducharme, Simon, Gerhard, Alexander, Danek, Adrian, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Le Ber, Isabelle, Pasquier, Florence, Rohrer, Jonathan D., Borroni, Barbara, Foster, Phoebe, Tiraboschi, Pietro, Esteve, Aitana Sogorb, Heller, Carolin, Greaves, Caroline V., Zetterberg, Henrik, Swift, Imogen J., Samra, Kiran, Shafei, Rachelle, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Papma, Janne M., Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B., Miltenberger, Gabriel, do Couto, Frederico Simões, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Repositório da Universidade de Lisboa, Bruffaerts, Rose, Genetic Frontotemporal dementia Initiative (GENFI), Neurology, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B, Miltenberger, Gabriel, do Couto, Frederico Simões, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Esteve, Aitana Sogorb, Heller, Carolin, Greaves, Caroline V, Zetterberg, Henrik, Swift, Imogen J, Samra, Kiran, Shafei, Rachelle, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Tiraboschi, Pietro, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Papma, Janne M, Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, and Borrego-Ecija, Sergi
Subjects: Serotonin, Positron emission tomography, Frontotemporal dementia, Frontotemporal lobar degeneration, Genes, Magnetic resonance imaging, Mutation, Neurotransmitters, C9orf72 Protein, Dopamine, Medizin, tau Proteins, diagnostic imaging [Frontotemporal Dementia], Acetylcholine, genetics [tau Proteins], methods [Magnetic Resonance Imaging], Pick Disease of the Brain, Neurology, ddc:570, Humans, Human medicine, genetics [Frontotemporal Dementia], genetics [C9orf72 Protein]
Abstract: Crown Copyright © 2023 Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)., Background: Neurotransmitters deficits in Frontotemporal Dementia (FTD) are still poorly understood. Better knowledge of neurotransmitters impairment, especially in prodromal disease stages, might tailor symptomatic treatment approaches. Methods: In the present study, we applied JuSpace toolbox, which allowed for cross-modal correlation of Magnetic Resonance Imaging (MRI)-based measures with nuclear imaging derived estimates covering various neurotransmitter systems including dopaminergic, serotonergic, noradrenergic, GABAergic and glutamatergic neurotransmission. We included 392 mutation carriers (157 GRN, 164 C9orf72, 71 MAPT), together with 276 non-carrier cognitively healthy controls (HC). We tested if the spatial patterns of grey matter volume (GMV) alterations in mutation carriers (relative to HC) are correlated with specific neurotransmitter systems in prodromal (CDR® plus NACC FTLD = 0.5) and in symptomatic (CDR® plus NACC FTLD≥1) FTD. Results: In prodromal stages of C9orf72 disease, voxel-based brain changes were significantly associated with spatial distribution of dopamine and acetylcholine pathways; in prodromal MAPT disease with dopamine and serotonin pathways, while in prodromal GRN disease no significant findings were reported (p < 0.05, Family Wise Error corrected). In symptomatic FTD, a widespread involvement of dopamine, serotonin, glutamate and acetylcholine pathways across all genetic subtypes was found. Social cognition scores, loss of empathy and poor response to emotional cues were found to correlate with the strength of GMV colocalization of dopamine and serotonin pathways (all p < 0.01). Conclusions: This study, indirectly assessing neurotransmitter deficits in monogenic FTD, provides novel insight into disease mechanisms and might suggest potential therapeutic targets to counteract disease-related symptoms., This work is supported by JPND grant “GENFI-prox” (2019–02248), the Centre d'Investigation Clinique (ICM, France) and the Centre pour l'Acquisition et le Traitement des Images platform (CATI, France), the UK Medical Research Council, the Italian Ministry of Health (CoEN015 and Ricerca Corrente), and the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, a Canadian Institutes of Health Research operating grant, and the Italian Ministry of Health (GR-2018-12365105). This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Alzheimer's Society grant (AS-PG-16-007), and the Bluefield Project. This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198).
Published: 2023

25. Language impairment in the genetic forms of behavioural variant frontotemporal dementia

Author: Samra, Kiran, MacDougall, Amy M., Bouzigues, Arabella, Bocchetta, Martina, Cash, David M., Greaves, Caroline V., Convery, Rhian S., van Swieten, John C., Seelaar, Harro, Jiskoot, Lize, Moreno, Fermin, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Sanchez-Valle, Raquel, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Laforce, Robert, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Graff, Caroline, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Masellis, Mario, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Tartaglia, Maria Carmela, Rowe, James B., Borroni, Barbara, Finger, Elizabeth, Synofzik, Matthis, Galimberti, Daniela, Vandenberghe, Rik, De Mendonça, Alexandre, Butler, Christopher R., Gerhard, Alexander, Ducharme, Simon, Le Ber, Isabelle, Tiraboschi, Pietro, Santana, Isabel, Pasquier, Florence, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Rohrer, Jonathan D., Russell, Lucy L., Nelson, Annabel, Thomas, David L., Todd, Emily, Benotmane, Hanya, Nicholas, Jennifer, Shafei, Rachelle, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Papma, Janne M., Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B., Miltenberger-Miltenyi, Gabriel, Simões Do Couto, Frederico, Neurology, Amsterdam Neuroscience - Neurodegeneration, Repositório da Universidade de Lisboa, Genetic FTD Initiative (GENFI), Erasmus MC other, Radiology & Nuclear Medicine, Clinical Genetics, Samra, Kiran [0000-0002-3105-7099], Apollo - University of Cambridge Repository, do Couto, Frederico Simões, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Nelson, Annabel, Thomas, David L, Todd, Emily, Benotmane, Hanya, Nicholas, Jennifer, Shafei, Rachelle, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Tiraboschi, Pietro, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Papma, Janne M, Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B, and Miltenberger, Gabriel
Subjects: Progranulin, Medizin, genetics [Mutation], tau Proteins, diagnostic imaging [Frontotemporal Dementia], frontotemporal dementia, Settore BIO/13 - Biologia Applicata, C9orf72, progranulin, Genetics, Humans, genetics, Language Development Disorders, ddc:610, tau, genetics [Frontotemporal Dementia], genetics [C9orf72 Protein], Frontotemporal dementia, Language, Tau, language, C9orf72 Protein, Magnetic Resonance Imaging, genetics [tau Proteins], Neurology, FOS: Biological sciences, Frontotemporal Dementia, Mutation, Human medicine, Neurology (clinical), Atrophy
Abstract: Funder: CIBERNED, Funder: Lemaire Family Foundation, Funder: Swedish Frontotemporal Dementia Initiative Schorling Foundation, Funder: Swedish Alzheimer Foundation, Funder: Karolinska Institutet; doi: http://dx.doi.org/10.13039/501100004047, Funder: Weston Brain Institute; doi: http://dx.doi.org/10.13039/100012479, Funder: Miriam Marks Brain Research UK, BACKGROUND: Behavioural variant fronto-temporal dementia (bvFTD) is characterised by a progressive change in personality in association with atrophy of the frontal and temporal lobes. Whilst language impairment has been described in people with bvFTD, little is currently known about the extent or type of linguistic difficulties that occur, particularly in the genetic forms. METHODS: Participants with genetic bvFTD along with healthy controls were recruited from the international multicentre Genetic FTD Initiative (GENFI). Linguistic symptoms were assessed using items from the Progressive Aphasia Severity Scale (PASS). Additionally, participants undertook the Boston Naming Test (BNT), modified Camel and Cactus Test (mCCT) and a category fluency test. Participants underwent a 3T volumetric T1-weighted MRI, with language network regional brain volumes measured and compared between the genetic groups and controls. RESULTS: 76% of the genetic bvFTD cohort had impairment in at least one language symptom: 83% C9orf72, 80% MAPT and 56% GRN mutation carriers. All three genetic groups had significantly impaired functional communication, decreased fluency, and impaired sentence comprehension. C9orf72 mutation carriers also had significantly impaired articulation and word retrieval as well as dysgraphia whilst the MAPT mutation group also had impaired word retrieval and single word comprehension. All three groups had difficulties with naming, semantic knowledge and verbal fluency. Atrophy in key left perisylvian language regions differed between the groups, with generalised involvement in the C9orf72 group and more focal temporal and insula involvement in the other groups. Correlates of language symptoms and test scores also differed between the groups. CONCLUSIONS: Language deficits exist in a substantial proportion of people with familial bvFTD across all three genetic groups. Significant atrophy is seen in the dominant perisylvian language areas and correlates with language impairments within each of the genetic groups. Improved understanding of the language phenotype in the main genetic bvFTD subtypes will be helpful in future studies, particularly in clinical trials where accurate stratification and monitoring of disease progression is required.
Published: 2023
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26. Interrupted CAG expansions in ATXN2 gene expand the genetic spectrum of frontotemporal dementias

Author: Clémence Fournier, Vincent Anquetil, Agnès Camuzat, Sandrine Stirati-Buron, Véronique Sazdovitch, Laura Molina-Porcel, Sabrina Turbant, Daisy Rinaldi, Raquel Sánchez-Valle, Mathieu Barbier, Morwena Latouche, Neuro-CEB Neuropathology Network, Giovanni Stevanin, Danielle Seilhean, Alexis Brice, Charles Duyckaerts, and Isabelle Le Ber
Subjects: Frontotemporal dementia, Frontotemporal lobar degeneration, TDP-43, Ataxin 2, Amyotrophic lateral sclerosis, C9orf72, Neurology. Diseases of the nervous system, RC346-429
Published: 2018
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27. Prodromal language impairment in genetic frontotemporal dementia within the GENFI cohort

Author: Samra, Kiran, primary, MacDougall, Amy M., additional, Bouzigues, Arabella, additional, Bocchetta, Martina, additional, Cash, David M., additional, Greaves, Caroline V., additional, Convery, Rhian S., additional, van Swieten, John C., additional, Jiskoot, Lize, additional, Seelaar, Harro, additional, Moreno, Fermin, additional, Sanchez-Valle, Raquel, additional, Laforce, Robert, additional, Graff, Caroline, additional, Masellis, Mario, additional, Tartaglia, Maria Carmela, additional, Rowe, James B., additional, Borroni, Barbara, additional, Finger, Elizabeth, additional, Synofzik, Matthis, additional, Galimberti, Daniela, additional, Vandenberghe, Rik, additional, de Mendonça, Alexandre, additional, Butler, Chris R., additional, Gerhard, Alex, additional, Ducharme, Simon, additional, Le Ber, Isabelle, additional, Tiraboschi, Pietro, additional, Santana, Isabel, additional, Pasquier, Florence, additional, Levin, Johannes, additional, Otto, Markus, additional, Sorbi, Sandro, additional, Rohrer, Jonathan D., additional, Russell, Lucy L., additional, Nelson, Annabel, additional, Thomas, David L., additional, Todd, Emily, additional, Benotmane, Hanya, additional, Nicholas, Jennifer, additional, Shafei, Rachelle, additional, Timberlake, Carolyn, additional, Cope, Thomas, additional, Rittman, Timothy, additional, Benussi, Alberto, additional, Premi, Enrico, additional, Gasparotti, Roberto, additional, Archetti, Silvana, additional, Gazzina, Stefano, additional, Cantoni, Valentina, additional, Arighi, Andrea, additional, Fenoglio, Chiara, additional, Scarpini, Elio, additional, Fumagalli, Giorgio, additional, Borracci, Vittoria, additional, Rossi, Giacomina, additional, Giaccone, Giorgio, additional, Di Fede, Giuseppe, additional, Caroppo, Paola, additional, Prioni, Sara, additional, Redaelli, Veronica, additional, Tang-Wai, David, additional, Rogaeva, Ekaterina, additional, Castelo-Branco, Miguel, additional, Freedman, Morris, additional, Keren, Ron, additional, Black, Sandra, additional, Mitchell, Sara, additional, Shoesmith, Christen, additional, Bartha, Robart, additional, Rademakers, Rosa, additional, Poos, Jackie, additional, Papma, Janne M., additional, Giannini, Lucia, additional, van Minkelen, Rick, additional, Pijnenburg, Yolande, additional, Nacmias, Benedetta, additional, Ferrari, Camilla, additional, Polito, Cristina, additional, Lombardi, Gemma, additional, Bessi, Valentina, additional, Veldsman, Michele, additional, Andersson, Christin, additional, Thonberg, Hakan, additional, Öijerstedt, Linn, additional, Jelic, Vesna, additional, Thompson, Paul, additional, Langheinrich, Tobias, additional, Lladó, Albert, additional, Antonell, Anna, additional, Olives, Jaume, additional, Balasa, Mircea, additional, Bargalló, Nuria, additional, Borrego-Ecija, Sergi, additional, Verdelho, Ana, additional, Maruta, Carolina, additional, Ferreira, Catarina B., additional, Miltenberger, Gabriel, additional, do Couto, Frederico Simões, additional, Gabilondo, Alazne, additional, Gorostidi, Ana, additional, Villanua, Jorge, additional, Cañada, Marta, additional, Tainta, Mikel, additional, Zulaica, Miren, additional, Barandiaran, Myriam, additional, Alves, Patricia, additional, Bender, Benjamin, additional, Wilke, Carlo, additional, Graf, Lisa, additional, Vogels, Annick, additional, Vandenbulcke, Mathieu, additional, Van Damme, Philip, additional, Bruffaerts, Rose, additional, Poesen, Koen, additional, Rosa-Neto, Pedro, additional, Gauthier, Serge, additional, Camuzat, Agnès, additional, Brice, Alexis, additional, Bertrand, Anne, additional, Funkiewiez, Aurélie, additional, Rinaldi, Daisy, additional, Saracino, Dario, additional, Colliot, Olivier, additional, Sayah, Sabrina, additional, Prix, Catharina, additional, Wlasich, Elisabeth, additional, Wagemann, Olivia, additional, Loosli, Sandra, additional, Schönecker, Sonja, additional, Hoegen, Tobias, additional, Lombardi, Jolina, additional, Anderl-Straub, Sarah, additional, Rollin, Adeline, additional, Kuchcinski, Gregory, additional, Bertoux, Maxime, additional, Lebouvier, Thibaud, additional, Deramecourt, Vincent, additional, Santiago, Beatriz, additional, Duro, Diana, additional, Leitão, Maria João, additional, Almeida, Maria Rosario, additional, Tábuas-Pereira, Miguel, additional, and Afonso, Sónia, additional
Published: 2023
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28. Temporal order of clinical and biomarker changes in familial frontotemporal dementia

Author: Staffaroni, Adam M, Quintana, Melanie, Heller, Carolin, Boeve, Bradley F, Rosen, Howard J, Rohrer, Jonathan D, Boxer, Adam L, Initiative, Frontotemporal Dementia Prevention, Apostolova, Liana, Barmada, Sami, Boeve, Bradley, Bozoki, Andrea, Clark, Annie L, Clark, David, Coppola, Giovanni, Darby, Ryan, Dickson, Dennis, Faber, Kelley, Fagan, Anne, Galasko, Douglas R, Grant, Ian M, Huang, Eric, Kerwin, Diana, Taylor, Jack Carson, Lapid, Maria, Lee, Suzee, Leger, Gabriel, Masdeux, Joseph C, McGinnis, Scott, Mendez, Mario, Onyike, Chiadi, Pascual, M Belen, Pressman, Peter, Rademakers, Rosa, Wise, Amy, Ramanan, Vijay, Ritter, Aaron, Seeley, William W, Syrjanen, Jeremy, Taylor, Jack C, Weintraub, Sandra, Esteve, Aitana Sogorb, Nelson, Annabel, Greaves, Caroline V, Thomas, David L, Ong, Elise, Benotmane, Hanya, Zetterberg, Henrik, Nicholas, Jennifer, Samra, Kiran, Shafei, Rachelle, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Forsberg, Leah, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Brushaber, Danielle, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Rojas, Julio C, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Poos, Jackie, Papma, Janne M, Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, VandeVrede, Lawren, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Ljubenkov, Peter, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B, Miltenberger, Gabriel, Wendelberger, Barbara, Kramer, Joel, Simões do Couto, Frederico, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Casaletto, Kaitlin B, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Appleby, Brian, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Bordelon, Yvette, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Botha, Hugo, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Dickerson, Bradford C, Domoto-Reilly, Kimiko, Fields, Julie A, Foroud, Tatiana, Gavrilova, Ralitza, Heuer, Hilary W, Geschwind, Daniel, Ghoshal, Nupur, Goldman, Jill, Graff-Radford, Jonathon, Graff-Radford, Neill, Grossman, Murray, Hall, Matthew G H, Hsiung, Ging-Yuek, Huey, Edward D, Irwin, David, Russell, Lucy L, Jones, David T, Kantarci, Kejal, Kaufer, Daniel, Knopman, David S, Kremers, Walter, Lago, Argentina Lario, Lapid, Maria I, Litvan, Irene, Lucente, Diane, Mackenzie, Ian R, Cobigo, Yann, Mendez, Mario F, Mester, Carly, Miller, Bruce L, Onyike, Chiadi U, Ramanan, Vijay K, Ramos, Eliana Marisa, Rao, Meghana, Rascovsky, Katya, Rankin, Katherine P, Wolf, Amy, Roberson, Erik D, Savica, Rodolfo, Tartaglia, M Carmela, Wong, Bonnie, Cash, David M, Bouzigues, Arabella, Swift, Imogen J, Peakman, Georgia, Bocchetta, Martina, Goh, Sheng-Yang Matt, Todd, Emily G, Convery, Rhian S, Rowe, James B, Borroni, Barbara, Galimberti, Daniela, Tiraboschi, Pietro, Masellis, Mario, Finger, Elizabeth, van Swieten, John C, Seelaar, Harro, Petrucelli, Leonard, Jiskoot, Lize C, Sorbi, Sandro, Butler, Chris R, Graff, Caroline, Gerhard, Alexander, Langheinrich, Tobias, Laforce, Robert, Sanchez-Valle, Raquel, de Mendonça, Alexandre, Moreno, Fermin, Gendron, Tania F, Synofzik, Matthis, Vandenberghe, Rik, Ducharme, Simon, Le Ber, Isabelle, Levin, Johannes, Danek, Adrian, Otto, Markus, Pasquier, Florence, Santana, Isabel, Kornak, John, Frontotemporal Dementia Prevention Initiative (FPI) Investigators, and Neurology
Subjects: Clinical Trials as Topic, C9orf72 Protein, biomarkers, genetics [Mutation], tau Proteins, General Medicine, Article, General Biochemistry, Genetics and Molecular Biology, genetics [tau Proteins], Chemistry, Frontotemporal Dementia, Mutation, Disease Progression, Humans, ddc:610, Human medicine, genetics [C9orf72 Protein], genetics [Frontotemporal Dementia], Biology, Biomarkers, dementia
Abstract: Data availability: The datasets analyzed for the current study reflect collaborative efforts of two research consortia: ALLFTD and GENFI. Each consortium provides clinical data access based on established policies for data use: processes for request are available for review at allftd.org/data for ALLFTD data and by emailing genfi@ucl.ac.uk. Certain data elements from both consortia (for example raw MRI images) may be restricted due to the potential for identifiability in the context of the sensitive nature of the genetic data. The deidentified combined dataset will be available for request through the FTD Prevention Initiative in 2023 (https://www.thefpi.org/). Code availability: Custom R code is available at https://doi.org/10.5281/zenodo.6687486. Copyright © The Author(s). Unlike familial Alzheimer’s disease, we have been unable to accurately predict symptom onset in presymptomatic familial frontotemporal dementia (f-FTD) mutation carriers, which is a major hurdle to designing disease prevention trials. We developed multimodal models for f-FTD disease progression and estimated clinical trial sample sizes in C9orf72, GRN and MAPT mutation carriers. Models included longitudinal clinical and neuropsychological scores, regional brain volumes and plasma neurofilament light chain (NfL) in 796 carriers and 412 noncarrier controls. We found that the temporal ordering of clinical and biomarker progression differed by genotype. In prevention-trial simulations using model-based patient selection, atrophy and NfL were the best endpoints, whereas clinical measures were potential endpoints in early symptomatic trials. f-FTD prevention trials are feasible but will likely require global recruitment efforts. These disease progression models will facilitate the planning of f-FTD clinical trials, including the selection of optimal endpoints and enrollment criteria to maximize power to detect treatment effects. Data collection and dissemination of the data presented in this paper were supported by the ALLFTD Consortium (U19: AG063911, funded by the National Institute on Aging and the National Institute of Neurological Diseases and Stroke) and the former ARTFL and LEFFTDS Consortia (ARTFL: U54 NS092089, funded by the National Institute of Neurological Diseases and Stroke and National Center for Advancing Translational Sciences; LEFFTDS: U01 AG045390, funded by the National Institute on Aging and the National Institute of Neurological Diseases and Stroke). The manuscript was reviewed by the ALLFTD Executive Committee for scientific content. The authors acknowledge the invaluable contributions of the study participants and families as well as the assistance of the support staffs at each of the participating sites. This work is also supported by the Association for Frontotemporal Degeneration (including the FTD Biomarkers Initiative), the Bluefield Project to Cure FTD, Larry L. Hillblom Foundation (2018-A-025-FEL (A.M.S.)), the National Institutes of Health (AG038791 (A.L.B.), AG032306 (H.J.R.), AG016976 (W.K.), AG062677 (Ron C. Peterson), AG019724 (B.L.M.), AG058233 (Suzee E. Lee), AG072122 (Walter Kukull), P30 AG062422 (B.L.M.), K12 HD001459 (N.G.), K23AG061253 (A.M.S.), AG062422 (RCP), K24AG045333 (H.J.R.)) and the Rainwater Charitable Foundation. Samples from the National Centralized Repository for Alzheimer Disease and Related Dementias (NCRAD), which receives government support under a cooperative agreement grant (U24 AG021886 (T.F.)) awarded by the National Institute on Aging (NIA), were used in this study. This work was also supported by Medical Research Council UK GENFI grant MR/M023664/1 (J.D.R.), the Bluefield Project, the National Institute for Health Research including awards to Cambridge and UCL Biomedical Research Centres and a JPND GENFI-PROX grant (2019–02248). Several authors of this publication are members of the European Reference Network for Rare Neurologic Diseases, project 739510. J.D.R. and L.L.R. are also supported by the National Institute for Health and Care Research (NIHR) UCL/H Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre Clinical Research Facility and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. J.D.R. is also supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). M.B. is supported by a Fellowship award from the Alzheimer’s Society, UK (AS-JF-19a-004-517). RC and C.G. are supported by a Frontotemporal Dementia Research Studentships in Memory of David Blechner funded through The National Brain Appeal (RCN 290173). J.B.R. is supported by NIHR Cambridge Biomedical Research Centre (BRC-1215-20014; the views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care), the Wellcome Trust (220258), the Cambridge Centre for Parkinson-plus and the Medical Research Council (SUAG/092 G116768); I.L.B. is supported by ANR-PRTS PREV-DemAls, PHRC PREDICT-PGRN, and several authors of this publication are members of the European Reference Network for Rare Neurological Diseases (project 739510). J.L. is funded by the Deutsche Forschungsgemeinschaft (German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198). R.S.-V. was funded at the Hospital Clinic de Barcelona by Instituto de Salud Carlos III, Spain (grant code PI20/00448 to RSV) and Fundació Marató TV3, Spain (grant code 20143810 to R.S.-V.). M.M. was, in part, funded by the UK Medical Research Council, the Italian Ministry of Health and the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, by Canadian Institutes of Health Research operating grants (MOP- 371851 and PJT-175242) and by funding from the Weston Brain Institute. R.L. is supported by the Canadian Institutes of Health Research and the Chaire de Recherche sur les Aphasies Primaires Progressives Fondation Famille Lemaire. C.G. is supported by the Swedish Frontotemporal Dementia Initiative Schörling Foundation, Swedish Research Council, JPND Prefrontals, 2015–02926,2018–02754, Swedish Alzheimer Foundation, Swedish Brain Foundation, Karolinska Institutet Doctoral Funding, KI Strat-Neuro, Swedish Dementia Foundation, and Stockholm County Council ALF/Region Stockholm. J.L. is supported by Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (German Research Foundation, EXC 2145 Synergy 390857198). The Dementia Research Centre is supported by Alzheimer’s Research UK, Alzheimer’s Society, Brain Research UK, and The Wolfson Foundation. This work was supported by the National Institute for Health Research UCL/H Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre Clinical Research Facility and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society, and Alzheimer’s Research UK.
Published: 2022

29. France: A Chronicle of French Family Law

Author: Bidaud-Garon, Christine, primary, Fulchiron, Hugues, additional, Baret, Bastien, additional, Camuzat, Aurore, additional, Fongaro, Eric, additional, and Millerioux, Guillaume, additional
Published: 2019
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30. Genetic forms of primary progressive aphasia within the GENetic Frontotemporal dementia Initiative (GENFI) cohort

Author: Samra, Kiran, MacDougall, Amy M, Bouzigues, Arabella, Bocchetta, Martina, Cash, David M, Greaves, Caroline V, Convery, Rhian S, Hardy, Chris, van Swieten, John C, Seelaar, Harro, Jiskoot, Lize C, Moreno, Fermin, Sanchez-Valle, Raquel, Laforce, Robert, Graff, Caroline, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B, Borroni, Barbara, Finger, Elizabeth, Synofzik, Matthis, Galimberti, Daniela, Vandenberghe, Rik, de Mendonça, Alexandre, Butler, Chris R, Gerhard, Alexander, Ducharme, Simon, Le Ber, Isabelle, Santana, Isabel, Pasquier, Florence, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Warren, Jason D, Rohrer, Jonathan D, Russell, Lucy L, Afonso, Sónia, Almeida, Maria Rosario, Anderl-Straub, Sarah, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Bertoux, Maxime, Bertrand, Anne, Bessi, Valentina, Black, Sandra, Borrego-Ecija, Sergi, Bras, Jose, Brice, Alexis, Bruffaerts, Rose, Camuzat, Agnès, Cañada, Marta, Cantoni, Valentina, Caroppo, Paola, Castelo-Branco, Miguel, Colliot, Olivier, Cope, Thomas, Deramecourt, Vincent, Arriba, María de, Fede, Giuseppe Di, Díez, Alina, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B, Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Funkiewiez, Aurélie, Cerveau, Institut du, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, Gazzina, Stefano, Giaccone, Giorgio, Gorostidi, Ana, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Karnath, Hans-Otto, Keren, Ron, Kuchcinski, Gregory, Langheinrich, Tobias, Lebouvier, Thibaud, João Leitão, Maria, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, Minkelen, Rick van, Mitchell, Sara, Moore, Katrina, Nacmias, Benedetta, Nelson, Annabel, Öijerstedt, Linn, Olives, Jaume, Ourselin, Sebastien, Padovani, Alessandro, Panman, Jessica, Papma, Janne M, Pijnenburg, Yolande, Polito, Cristina, Premi, Enrico, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rinaldi, Daisy, Rittman, Tim, Rogaeva, Ekaterina, Rollin, Adeline, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Saracino, Dario, Sayah, Sabrina, Scarpini, Elio, Schönecker, Sonja, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Swift, Imogen, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Tang-Wai, David, Thomas, David L, Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Todd, Emily, Damme, Philip Van, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, GENetic Frontotemporal dementia Initiative (GENFI), Bruffaerts, Rose, Bocchetta, Martina [0000-0003-1814-5024], Cash, David M [0000-0001-7833-616X], Seelaar, Harro [0000-0003-1989-7527], Jiskoot, Lize C [0000-0002-1120-1858], Sanchez-Valle, Raquel [0000-0001-7750-896X], Graff, Caroline [0000-0002-9949-2951], Borroni, Barbara [0000-0001-9340-9814], Synofzik, Matthis [0000-0002-2280-7273], Vandenberghe, Rik [0000-0001-6237-2502], Gerhard, Alexander [0000-0002-8071-6062], Ducharme, Simon [0000-0002-7309-1113], Pasquier, Florence [0000-0001-9880-9788], Apollo - University of Cambridge Repository, Neurology, Meeter, Lieke, Miltenberger, Gabriel, van Minkelen, Rick, Mitchell, Sara, Moore, Katrina, Nacmias, Benedetta, Nelson, Annabel, Öijerstedt, Linn, Olives, Jaume, Ourselin, Sebastien, Padovani, Alessandro, Panman, Jessica, Papma, Janne M, Pijnenburg, Yolande, Polito, Cristina, Premi, Enrico, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rinaldi, Daisy, du Cerveau, Institut, Rittman, Tim, Rogaeva, Ekaterina, Rollin, Adeline, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Saracino, Dario, Sayah, Sabrina, Scarpini, Elio, Schönecker, Sonja, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Swift, Imogen, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Tang-Wai, David, Thomas, David L, Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Todd, Emily, Damme, Philip Van, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Afonso, Sónia, Almeida, Maria Rosario, Anderl-Straub, Sarah, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Bertoux, Maxime, Bertrand, Anne, Bessi, Valentina, Black, Sandra, Borrego-Ecija, Sergi, Bras, Jose, Brice, Alexis, Camuzat, Agnès, Cañada, Marta, Cantoni, Valentina, Caroppo, Paola, Castelo-Branco, Miguel, Colliot, Olivier, Cope, Thomas, Deramecourt, Vincent, de Arriba, María, Fede, Giuseppe Di, Díez, Alina, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B, Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Funkiewiez, Aurélie, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, Gazzina, Stefano, Giaccone, Giorgio, Gorostidi, Ana, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Karnath, Hans-Otto, Keren, Ron, Kuchcinski, Gregory, Langheinrich, Tobias, Lebouvier, Thibaud, João Leitão, Maria, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, and Mead, Simon
Subjects: Cellular and Molecular Neuroscience, Psychiatry and Mental health, Neurology, SDG 3 - Good Health and Well-being, Medizin, MAPT, primary progressive aphasia, ddc:610, c9orf72, GRN, Biological Psychiatry
Abstract: Funder: Alzheimer's Research UK, Funder: Bluefield Project, Funder: Royal National Institute, Funder: Weston Brain Institute and Ontario Brain Institute, Funder: Alzheimer Nederland and the Bluefield, Funder: Alzheimer's Society, Funder: Dementia Research Centre, Funder: Medical Research Council, Funder: National Institute for Health Research University College London/Hospitals Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre Clinical Research Facility, Funder: Alzheimer Foundation, Funder: Alzheimer's Society and Alzheimer's Research UK, Funder: Association for Frontotemporal Dementias Research Grant 2009, Funder: Brain Research UK, Funder: Dementia Research Institute Ltd, Funder: The Wolfson Foundation, Funder: UK Dementia Research Institute, Funder: UK Dementia Research Institute Ltd, Funder: Deaf People Dunhill Medical Trust Pauline Ashley Fellowship, Funder: Frontotemporal Dementia Research Studentships, Funder: Germany’s Federal Ministry of Education and Research, Funder: Miriam Marks Brain Research UK Senior Fellowship, Funder: Tau Consortium and the Center for Networked Biomedical Research, Funder: Mady Browaeys Fund for Research into Frontotemporal Dementia, Funder: Brain Foundation and Stockholm County Council ALF, Funder: Deutsche Forschungsgemeinschaft German Research Foundation under Germany’s Excellence Strategy, Funder: Alzheimer’s Research UK, Funder: Memory of David Blechner, Funder: Swedish FTD Inititative-Schörling Foundation, Primary progressive aphasia is most commonly a sporadic disorder, but in some cases, it can be genetic. This study aimed to understand the clinical, cognitive and imaging phenotype of the genetic forms of primary progressive aphasia in comparison to the canonical nonfluent, semantic and logopenic subtypes seen in sporadic disease. Participants with genetic primary progressive aphasia were recruited from the international multicentre GENetic Frontotemporal dementia Initiative study and compared with healthy controls as well as a cohort of people with sporadic primary progressive aphasia. Symptoms were assessed using the GENetic Frontotemporal dementia Initiative language, behavioural, neuropsychiatric and motor scales. Participants also underwent a cognitive assessment and 3 T volumetric T1-weighted MRI. One C9orf72 (2%), 1 MAPT (6%) and 17 GRN (44%) symptomatic mutation carriers had a diagnosis of primary progressive aphasia. In the GRN cohort, 47% had a diagnosis of nonfluent variant primary progressive aphasia, and 53% had a primary progressive aphasia syndrome that did not fit diagnostic criteria for any of the three subtypes, called primary progressive aphasia-not otherwise specified here. The phenotype of the genetic nonfluent variant primary progressive aphasia group largely overlapped with that of sporadic nonfluent variant primary progressive aphasia, although the presence of an associated atypical parkinsonian syndrome was characteristic of sporadic and not genetic disease. The primary progressive aphasia -not otherwise specified group however was distinct from the sporadic subtypes with impaired grammar/syntax in the presence of relatively intact articulation, alongside other linguistic deficits. The pattern of atrophy seen on MRI in the genetic nonfluent variant primary progressive aphasia group overlapped with that of the sporadic nonfluent variant primary progressive aphasia cohort, although with more posterior cortical involvement, whilst the primary progressive aphasia-not otherwise specified group was strikingly asymmetrical with involvement particularly of the insula and dorsolateral prefrontal cortex but also atrophy of the orbitofrontal cortex and the medial temporal lobes. Whilst there are overlapping symptoms between genetic and sporadic primary progressive aphasia syndromes, there are also distinct features. Future iterations of the primary progressive aphasia consensus criteria should encompass such information with further research needed to understand the earliest features of these disorders, particularly during the prodromal period of genetic disease.
Published: 2023

31. Structural MRI predicts clinical progression in presymptomatic genetic frontotemporal dementia: findings from the GENetic Frontotemporal dementia Initiative cohort

Author: Bocchetta, Martina, Todd, Emily G, Bouzigues, Arabella, Cash, David M, Nicholas, Jennifer M, Convery, Rhian S, Russell, Lucy L, Thomas, David L, Malone, Ian B, Iglesias, Juan Eugenio, Van Swieten, John C, Jiskoot, Lize C, Seelaar, Harro, Borroni, Barbara, Galimberti, Daniela, Sanchez-Valle, Raquel, Laforce, Robert, Moreno, Fermin, Synofzik, Matthis, Graff, Caroline, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B, Vandenberghe, Rik, Finger, Elizabeth, Tagliavini, Fabrizio, De Mendonca, Alexandre, Santana, Isabel, Butler, Chris R, Ducharme, Simon, Gerhard, Alexander, Danek, Adrian, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Le Ber, Isabelle, Pasquier, Florence, Rohrer, Jonathan D, Esteve, Aitana Sogorb, Nelson, Annabel, Heller, Carolin, Greaves, Caroline V, Benotmane, Hanya, Zetterberg, Henrik, Swift, Imogen J, Samra, Kiran, Shafei, Rachelle, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Tiraboschi, Pietro, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Papma, Janne M, Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B, Miltenberger, Gabriel, Simões do Couto, Frederico, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Bocchetta, Martina [0000-0003-1814-5024], Todd, Emily G [0000-0003-1551-5691], Cash, David M [0000-0001-7833-616X], Malone, Ian B [0000-0001-7512-7856], Jiskoot, Lize C [0000-0002-1120-1858], Seelaar, Harro [0000-0003-1989-7527], Borroni, Barbara [0000-0001-9340-9814], Sanchez-Valle, Raquel [0000-0001-7750-896X], Synofzik, Matthis [0000-0002-2280-7273], Graff, Caroline [0000-0002-9949-2951], Vandenberghe, Rik [0000-0001-6237-2502], Ducharme, Simon [0000-0002-7309-1113], Gerhard, Alexander [0000-0002-8071-6062], Danek, Adrian [0000-0001-8857-5383], Pasquier, Florence [0000-0001-9880-9788], Apollo - University of Cambridge Repository, Genetic Frontotemporal dementia Initiative (GENFI), Neurology, Bargalló, Nuria, Borrego-Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B, Miltenberger, Gabriel, Simões do Couto, Frederico, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Esteve, Aitana Sogorb, Nelson, Annabel, Heller, Carolin, Greaves, Caroline V, Benotmane, Hanya, Zetterberg, Henrik, Swift, Imogen J, Samra, Kiran, Shafei, Rachelle, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Tiraboschi, Pietro, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Papma, Janne M, Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, and Balasa, Mircea
Subjects: Cellular and Molecular Neuroscience, Psychiatry and Mental health, Neurology, SDG 3 - Good Health and Well-being, brain volumetry, diffusion imaging, genetic frontotemporal dementia, MRI imaging, Medizin, presymptomatic stage, ddc:610, Biological Psychiatry
Abstract: Funder: Deutsche Forschungsgemeinschaft, Funder: Dementia Research Institute, Funder: Leonard Wolfson Experimental Neurology Centre, Funder: Canadian Institutes of Health Research, Funder: Medical Research Council, Funder: Miriam Marks Brain Research UK Senior Fellowship, Funder: Wolfson Foundation, Funder: Mady Browaeys Fonds voor Onderzoek naar Frontotemporale Degeneratie, Funder: NVIDIA, Funder: Alzheimer's Research UK, Funder: Alzheimer's Society and Alzheimer's Research, Funder: Brain Research UK, Funder: University College London, Biomarkers that can predict disease progression in individuals with genetic frontotemporal dementia are urgently needed. We aimed to identify whether baseline MRI-based grey and white matter abnormalities are associated with different clinical progression profiles in presymptomatic mutation carriers in the GENetic Frontotemporal dementia Initiative. Three hundred eighty-seven mutation carriers were included (160 GRN, 160 C9orf72, 67 MAPT), together with 240 non-carrier cognitively normal controls. Cortical and subcortical grey matter volumes were generated using automated parcellation methods on volumetric 3T T1-weighted MRI scans, while white matter characteristics were estimated using diffusion tensor imaging. Mutation carriers were divided into two disease stages based on their global CDR®+NACC-FTLD score: presymptomatic (0 or 0.5) and fully symptomatic (1 or greater). The w-scores in each grey matter volumes and white matter diffusion measures were computed to quantify the degree of abnormality compared to controls for each presymptomatic carrier, adjusting for their age, sex, total intracranial volume, and scanner type. Presymptomatic carriers were classified as 'normal' or 'abnormal' based on whether their grey matter volume and white matter diffusion measure w-scores were above or below the cut point corresponding to the 10th percentile of the controls. We then compared the change in disease severity between baseline and one year later in both the 'normal' and 'abnormal' groups within each genetic subtype, as measured by the CDR®+NACC-FTLD sum-of-boxes score and revised Cambridge Behavioural Inventory total score. Overall, presymptomatic carriers with normal regional w-scores at baseline did not progress clinically as much as those with abnormal regional w-scores. Having abnormal grey or white matter measures at baseline was associated with a statistically significant increase in the CDR®+NACC-FTLD of up to 4 points in C9orf72 expansion carriers, and 5 points in the GRN group as well as a statistically significant increase in the revised Cambridge Behavioural Inventory of up to 11 points in MAPT, 10 points in GRN, and 8 points in C9orf72 mutation carriers. Baseline regional brain abnormalities on MRI in presymptomatic mutation carriers are associated with different profiles of clinical progression over time. These results may be helpful to inform stratification of participants in future trials.
Published: 2023

32. Neurodevelopmental effects of genetic frontotemporal dementia in young adult mutation carriers

Author: Finger, Elizabeth, Malik, Rubina, Bocchetta, Martina, Coleman, Kristy, Graff, Caroline, Borroni, Barbara, Masellis, Mario, Laforce, Robert, Greaves, Caroline V., Russell, Lucy L., Convery, Rhian S., Bouzigues, Arabella, Cash, David M., Otto, Markus, Synofzik, Matthis, Rowe, James B., Galimberti, Daniela, Tiraboschi, Pietro, Bartha, Robert, Shoesmith, Christen, Tartaglia, Maria Carmela, van Swieten, John C., Seelaar, Harro, Jiskoot, Lize C., Sorbi, Sandro, Butler, Chris R., Gerhard, Alexander, Sanchez-Valle, Raquel, De Mendonça, Alexandre, Moreno, Fermin, Vandenberghe, Rik, Le Ber, Isabelle, Levin, Johannes, Pasquier, Florence, Santana, Isabel, Rohrer, Jonathan D., Ducharme, Simon, Esteve, Aitana Sogorb, Heller, Carolin, Thomas, David L., Todd, Emily G., Nicholas, Jennifer, Benotmane, Hanya, Zetterberg, Henrik, Swift, Imogen J., Samra, Kiran, Shafei, Rachelle, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Rademakers, Rosa, Poos, Jackie, Papma, Janne M., Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B., Miltenberger-Miltenyi, Gabriel, Simões Do Couto, Frederico, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Genetic FTD Initiative, GENFI, the Genetic FTD Initiative (GENFI), Repositório da Universidade de Lisboa, Bocchetta, Martina [0000-0003-1814-5024], Graff, Caroline [0000-0002-9949-2951], Borroni, Barbara [0000-0001-9340-9814], Cash, David M [0000-0001-7833-616X], Synofzik, Matthis [0000-0002-2280-7273], Seelaar, Harro [0000-0003-1989-7527], Jiskoot, Lize C [0000-0002-8120-7366], Gerhard, Alexander [0000-0002-8071-6062], Sanchez-Valle, Raquel [0000-0001-7750-896X], Vandenberghe, Rik [0000-0001-6237-2502], Pasquier, Florence [0000-0001-9880-9788], Ducharme, Simon [0000-0002-7309-1113], Apollo - University of Cambridge Repository, Neurology, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B, Miltenberger, Gabriel, do Couto, Frederico Simões, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Esteve, Aitana Sogorb, Heller, Carolin, Thomas, David L, Todd, Emily G, Nicholas, Jennifer, Benotmane, Hanya, Zetterberg, Henrik, Swift, Imogen J, Samra, Kiran, Shafei, Rachelle, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Tiraboschi, Pietro, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Rademakers, Rosa, Poos, Jackie, Papma, Janne M, Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, and Borrego-Ecija, Sergi
Subjects: Adult, C9orf72 Protein, neurodevelopment, Nocturnal pulsed oximetry, Medizin, Brain, Neurodegenerative Diseases, tau Proteins, Amyotrophic lateral sclerosis, frontotemporal dementia, Phrenic nerve, Young Adult, Progranulins, Pick Disease of the Brain, Respiratory tests, Mutation, C9orf72, MAPT, Humans, ddc:610, Neurology (clinical), Human medicine, GRN, Respiratory function
Abstract: © The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved., While frontotemporal dementia has been considered a neurodegenerative disease that starts in mid-life or later, it is now clearly established that cortical and subcortical volume loss is observed more than a decade prior to symptom onset and progresses with ageing. To test the hypothesis that genetic mutations causing frontotemporal dementia have neurodevelopmental consequences, we examined the youngest adults in the GENFI cohort of pre-symptomatic frontotemporal dementia mutation carriers who are between 19 and 30 years of age. Structural brain differences and improved performance on some cognitive tests were found for MAPT and GRN mutation carriers relative to familial non-carriers, while smaller volumes were observed in C9orf72 repeat expansion carriers at a mean age of 26 years. The detection of such early differences supports potential advantageous neurodevelopmental consequences of some frontotemporal dementia-causing genetic mutations. These results have implications for the design of therapeutic interventions for frontotemporal dementia. Future studies at younger ages are needed to identify specific early pathophysiologic or compensatory processes that occur during the neurodevelopmental period., This project was supported by Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, and by Canadian Institutes of Health Research operating grants (327387; 452843; 70797). The Dementia Research Centre is supported by Alzheimer’s Research UK, Alzheimer’s Society, Brain Research UK, and The Wolfson Foundation. This work was supported by the National Institute for Health Research (NIHR) Queen Square Dementia Biomedical Research Unit and the University College London Hospitals Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC), and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Italian Ministry of Health (CoEN015 and Ricerca Corrente), the Alzheimer’s Society grant (AS-PG-16-007), the Bluefield Project and the EU Joint Programme – Neurodegenerative Disease Research (GENFI-PROX grant 2019-02248). M.B. is supported by a Fellowship award from the Alzheimer’s Society, UK (AS-JF-19a- 004-517). M.B.’s work was also supported by the UK Dementia Research Institute which receives its funding from DRI Ltd., funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. J.D.R. is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). J.B.R. is funded by the Wellcome Trust (103838) and the National Institute for Health Research Cambridge Biomedical Research Centre. This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198). It is also funded by the Ministry of Health, Italy (S.S.). R.V.’s work is supported by the Mady Browaeys Fonds voor Onderzoek naar Frontotemporale Degeneratie. R.S.-V.’s work is supported by Instituto de Salud Carlos III (grant number 20/00448), cofunded by the EU. ANR-PRTS PrevdemALS study funding (I.L.B.). Several authors of this publication (J.C.vS., M.S., A.D., M.O., R.V., I.L.B., J.D.R.) are members of the European Reference Network for Rare Neurological Diseases (ERN-RND) - Project ID No 739510.
Published: 2023

33. C9ORF72 knockdown triggers FTD-like symptoms and cell pathology in mice

Author: Lopez-Herdoiza, Maria-Belen, primary, Bauché, Stephanie, additional, Wilmet, Baptiste, additional, Le Duigou, Caroline, additional, Roussel, Delphine, additional, Frah, Magali, additional, Béal, Jonas, additional, Devely, Gabin, additional, Boluda, Susana, additional, Frick, Petra, additional, Bouteiller, Delphine, additional, Dussaud, Sébastien, additional, Guillabert, Pierre, additional, Dalle, Carine, additional, Dumont, Magali, additional, Camuzat, Agnes, additional, Saracino, Dario, additional, Barbier, Mathieu, additional, Bruneteau, Gaelle, additional, Ravassard, Phillippe, additional, Neumann, Manuela, additional, Nicole, Sophie, additional, Le Ber, Isabelle, additional, Brice, Alexis, additional, and Latouche, Morwena, additional
Published: 2023
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34. Integrative genetic analysis illuminates ALS heritability and identifies risk genes

Author: Neurogenetica, Brain, Genetic Risks, Neurologen, Megat, Salim, Mora, Natalia, Sanogo, Jason, Roman, Olga, Catanese, Alberto, Alami, Najwa Ouali, Freischmidt, Axel, Mingaj, Xhuljana, De Calbiac, Hortense, Muratet, François, Dirrig-Grosch, Sylvie, Dieterle, Stéphane, Van Bakel, Nick, Müller, Kathrin, Sieverding, Kirsten, Weishaupt, Jochen, Andersen, Peter Munch, Weber, Markus, Neuwirth, Christoph, Margelisch, Markus, Sommacal, Andreas, Van Eijk, Kristel R., Veldink, Jan H., Lautrette, Géraldine, Couratier, Philippe, Camuzat, Agnès, Le Ber, Isabelle, Grassano, Maurizio, Chio, Adriano, Boeckers, Tobias, Ludolph, Albert C., Roselli, Francesco, Yilmazer-Hanke, Deniz, Millecamps, Stéphanie, Kabashi, Edor, Storkebaum, Erik, Sellier, Chantal, Dupuis, Luc, Project MinE ALS Sequencing Consortium, Neurogenetica, Brain, Genetic Risks, Neurologen, Megat, Salim, Mora, Natalia, Sanogo, Jason, Roman, Olga, Catanese, Alberto, Alami, Najwa Ouali, Freischmidt, Axel, Mingaj, Xhuljana, De Calbiac, Hortense, Muratet, François, Dirrig-Grosch, Sylvie, Dieterle, Stéphane, Van Bakel, Nick, Müller, Kathrin, Sieverding, Kirsten, Weishaupt, Jochen, Andersen, Peter Munch, Weber, Markus, Neuwirth, Christoph, Margelisch, Markus, Sommacal, Andreas, Van Eijk, Kristel R., Veldink, Jan H., Lautrette, Géraldine, Couratier, Philippe, Camuzat, Agnès, Le Ber, Isabelle, Grassano, Maurizio, Chio, Adriano, Boeckers, Tobias, Ludolph, Albert C., Roselli, Francesco, Yilmazer-Hanke, Deniz, Millecamps, Stéphanie, Kabashi, Edor, Storkebaum, Erik, Sellier, Chantal, Dupuis, Luc, and Project MinE ALS Sequencing Consortium
Published: 2023

35. Integrative genetic analysis illuminates ALS heritability and identifies risk genes

Author: Megat, S., Mora, N., Sanogo, J., Roman, O., Catanese, A., Alami, N.O., Freischmidt, A., Mingaj, X., Calbiac, H. De, Muratet, F., Dirrig-Grosch, S., Dieterle, S., Bakel, N. Van, Muller, K., Sieverding, K., Weishaupt, J., Andersen, P.M., Weber, M., Neuwirth, C., Margelisch, M., Sommacal, A., Eijk, K.R. van, Veldink, J.H., Lautrette, G., Couratier, P., Camuzat, A., Ber, I. Le, Grassano, M., Chio, A., Boeckers, T., Ludolph, A.C., Roselli, F., Yilmazer-Hanke, D., Millecamps, S., Kabashi, E., Storkebaum, E.J.M., Sellier, C., Dupuis, L., Megat, S., Mora, N., Sanogo, J., Roman, O., Catanese, A., Alami, N.O., Freischmidt, A., Mingaj, X., Calbiac, H. De, Muratet, F., Dirrig-Grosch, S., Dieterle, S., Bakel, N. Van, Muller, K., Sieverding, K., Weishaupt, J., Andersen, P.M., Weber, M., Neuwirth, C., Margelisch, M., Sommacal, A., Eijk, K.R. van, Veldink, J.H., Lautrette, G., Couratier, P., Camuzat, A., Ber, I. Le, Grassano, M., Chio, A., Boeckers, T., Ludolph, A.C., Roselli, F., Yilmazer-Hanke, D., Millecamps, S., Kabashi, E., Storkebaum, E.J.M., Sellier, C., and Dupuis, L.
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Published: 2023

36. MACVIA clinical decision algorithm in adolescents and adults with allergic rhinitis

Author: Aberer, Werner, Adachi, Mitsuru, Agache, Ioana, Akdis, Cezmi, Akdis, Mubeccel, Annesi-Maesano, Isabella, Ansotegui, Ignacio J., Anto, Josep M., Arshad, S. Hasan, Baiardini, Ilaria, Baigenzhin, Abay K., Barbara, Cristina, Bateman, Eric D., Beghé, Bianca, Bel, Elisabeth H., Ben Kheder, Ali, Bennoor, Kazi S., Benson, Michael, Bernstein, David, Michael, Bewick, Thomas, Bieber, Bindslev-Jensen, Carsten, Bjermer, Leif, Blain, Hubert, Boner, Attilio, Bonini, Matteo, Bonini, Sergio, Bosse, Isabelle, Bouchard, Jacques, Boulet, Louis-Philippe, Bourret, Rodolphe A., Bousquet, Philippe J., Braido, Fulvio, Briggs, Andrew H., Brightling, Christopher E., Buhl, Roland, Burney, Peter, Bush, Andrew, Caballero-Fonseca, Fernando, Caimmi, Davide P., Camargos, Paulo, Camuzat, Thierry, Carlsen, Kai-Hakon, Carr, Warner, Casale, Thomas B., Sarabia, Alfonso Cepeda, Chatzi, Leda, Chen, Yuzhi, Chiron, Raphaël, Chkhartishvili, Ekaterine, Chuchalin, Alexander, Ciprandi, Georgio, Cirule, Ieva, Correia de Sousa, Jaime, Costa, David, Crooks, George, Custovic, Adnan, Dahlen, Sven-Erik, Darsow, Ulf, De Blay, Frédéric, De Manuel Keenoy, Esteban, Dedeu, Tony, Deleanu, Diana, Denburg, Judah, Didier, Alain, Dinh-Xuan, Anh-Tuan, Dokic, Dejan, Douagui, Habib B., Dubakiene, Ruta, Durham, Stephen, Dykewicz, Mark, El-Gamal, Yehia, Emuzyte, Regina, Fink-Wagner, Antje, Fiocchi, Alessandro, Forastiere, Francesco, Gamkrelidze, Amiran, Gemicioğlu, Bilun, Gereda, Jose E., Gerth van Wijk, Roy, Gotua, Maia, Grisle, Ineta, Guzmán, M. Antonieta, Haahtela, Tari, Heinrich, Joachim, Hellquist-Dahl, Birthe, Horak, Friedrich, Howarth, Peter H., Humbert, Marc, Hyland, Michael, Ivancevich, Juan-Carlos, Jares, Edgardo J., Johnston, Sebastian L., Jonquet, Olivier, Joos, Guy, Jung, Ki-Suck, Just, Jocelyne, Jutel, Marek, Kaidashev, Igor P., Khaitov, Musa, Kalayci, Omer, Kalyoncu, Fuat, Keith, Paul, Khaltaev, Nikolai, Kleine-Tebbe, Jorg, Klimek, Ludger, N'Goran, Bernard Koffi, Kolek, Vitezlav, Koppelman, Gerard H., Kowalski, Marek, Kull, Inger, Kvedariene, Violeta, Lambrecht, Bart, Lau, Susanne, Laune, Daniel, Le Thi Tuyet, Lan, Li, Jing, Lieberman, Phillipe, Lipworth, Brian J., Renaud, Louis, Magard, Yves, Magnan, Antoine, Mahboub, Bassam, Majer, Ivan, Makela, Mika, Manning, Peter J., Masjedi, Mohamad R., Maurer, Marcus, Mavale-Manuel, Sandra, Melén, Erik, Melo-Gomes, Elisabete, Mercier, Jacques, Merk, Hans, Miculinic, Neven, Mihaltan, Florin, Milenkovic, Branislava, Mohammad, Yousser, Molimard, Mathieu, Momas, Isabelle, Montilla-Santana, Anna, Morais-Almeida, Mario, Mösges, Ralph, Nadif, Rachel, Namazova-Baranova, Leyla, Neffen, Hugo, Nekam, Kristof, Neou, Angelos, Niggemann, Bodo, Nyembue, Dieudonné, O'Hehir, Robyn, Ohta, Ken, Okamoto, Yoshitaka, Okubo, Kim, Ouedraogo, Solange, Paggiaro, Pier-Luigi, Pali-Schöll, Isabella, Palmer, Stephen, Panzner, Petr, Papi, Alberto, Park, Hae-Sim, Pavord, Ian, Pawankar, Ruby, Pfaar, Oliver, Picard, Robert, Pigearias, Bernard, Pin, Isabelle, Plavec, Davor, Pohl, Wolfgang, Popov, Todor, Postma, Dirkje S., Potter, Paul, Poulsen, Lars K., Rabe, Klaus F., Raciborski, Filip, Pontal, Françoise Radier, Reitamo, Sakari, Repka-Ramirez, Maria-Susana, Robalo-Cordeiro, Carlos, Roberts, Graham, Rodenas, Francisco, Rolland, Christine, Rodriguez, Miguel Roman, Romano, Antonino, Rosado-Pinto, José, Rosario, Nelson A., Rosenwasser, Larry, Rottem, Menachem, Sanchez-Borges, Mario, Sastre-Dominguez, Joaquim, Schmid-Grendelmeier, Peter, Serrano, Eli, Simons, F. Estelle R., Sisul, Juan-Carlos, Skrindo, Ingebjorg, Smit, Henriette A., Solé, Dirceu, Sooronbaev, Talant, Spranger, Otto, Stelmach, Rafael, Strandberg, Timo, Sunyer, Jordi, Thijs, Carel, Todo-Bom, Ana-Maria, Triggiani, Massimo, Valenta, Rudolf, Valero, Antonio L., van Hage, Marianne, Vandenplas, Olivier, Vezzani, Giorgio, Vichyanond, Pakit, Viegi, Giovanni, Wagenmann, Martin, Wahn, Ulrich, De Yun, Wang, Williams, Denis, Wright, John, Yawn, Barbara P., Yiallouros, Panayiotis, Yusuf, Osman M., Zar, Heather J., Zernotti, Mario, Zhang, Luo, Zhong, Nanshan, Zidarn, Mihaela, Bousquet, Jean, Schünemann, Holger J., Hellings, Peter W., Arnavielhe, Sylvie, Bachert, Claus, Bedbrook, Anna, Bergmann, Karl-Christian, Bosnic-Anticevich, Sinthia, Brozek, Jan, Calderon, Moises, Canonica, G. Walter, Chavannes, Niels H., Cox, Linda, Chrystyn, Henry, Cruz, Alvaro A., Dahl, Ronald, De Carlo, Giuseppe, Demoly, Pascal, Devillier, Phillipe, Dray, Gérard, Fletcher, Monica, Fokkens, Wytske J., Fonseca, Joao, Gonzalez-Diaz, Sandra N., Grouse, Lawrence, Keil, Thomas, Kuna, Piotr, Larenas-Linnemann, Désirée, Lodrup Carlsen, Karin C., Meltzer, Eli O., Mullol, Jaoquim, Muraro, Antonella, Naclerio, Robert N., Palkonen, Susanna, Papadopoulos, Nikolaos G., Passalacqua, Giovanni, Price, David, Ryan, Dermot, Samolinski, Boleslaw, Scadding, Glenis K., Sheikh, Aziz, Spertini, François, Valiulis, Arunas, Valovirta, Erkka, Walker, Samantha, Wickman, Magnus, Yorgancioglu, Arzu, and Zuberbier, Torsten
Published: 2016
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37. Temporal dynamics predict symptom onset and cognitive decline in familial frontotemporal dementia

Author: Whiteside, David J, Malpetti, Maura, Jones, P Simon, Ghosh, Boyd CP, Coyle‐Gilchrist, Ian, van Swieten, John C, Seelaar, Harro, Jiskoot, Lize, Borroni, Barbara, Sanchez‐Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Synofzik, Matthis, Galimberti, Daniela, Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, Vandenberghe, Rik, de Mendonça, Alexandre, Tagliavini, Fabrizio, Butler, Chris R, Santana, Isabel, Ber, Isabelle Le, Gerhard, Alexander, Ducharme, Simon, Levin, Johannes, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Pasquier, Florence, Bouzigues, Arabella, Russell, Lucy L, Rohrer, Jonathan D, Rowe, James B, Rittman, Timothy, Esteve, Aitana Sogorb, Nelson, Annabel, Heller, Carolin, Greaves, Caroline V, Cash, David, Thomas, David L, Todd, Emily, Benotmane, Hanya, Zetterberg, Henrik, Swift, Imogen J, Nicholas, Jennifer, Samra, Kiran, Bocchetta, Martina, Shafei, Rachelle, Convery, Rhian S, Timberlake, Carolyn, Cope, Thomas, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Tiraboschi, Pietro, Prioni, Sara, Redaelli, Veronica, Tang‐Wai, David, Rogaeva, Ekaterina, Castelo‐Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Papma, Janne M, Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego‐Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B, Miltenberger, Gabriel, Simões do Couto, Frederico, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa‐Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl‐Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas‐Pereira, Miguel, Afonso, Sónia, Engel, Annerose, Polyakova, Maryna, Whiteside, David [0000-0002-5890-9220], Apollo - University of Cambridge Repository, GENFI Consortium, Repositório da Universidade de Lisboa, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B, Miltenberger, Gabriel, Simões do Couto, Frederico, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Engel, Annerose, Polyakova, Maryna, Esteve, Aitana Sogorb, Nelson, Annabel, Bouzigues, Arabella, Heller, Carolin, Greaves, Caroline V, Cash, David, Thomas, David L, Todd, Emily, Benotmane, Hanya, Zetterberg, Henrik, Swift, Imogen J, Nicholas, Jennifer, Samra, Kiran, Russell, Lucy L, Bocchetta, Martina, Shafei, Rachelle, Convery, Rhian S, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Tiraboschi, Pietro, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Papma, Janne M, Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, and Neurology
Subjects: Epidemiology, FEATURED ARTICLE, Medizin, Clinical Neurology, NETWORK CONNECTIVITY, frontotemporal dementia, disease progression, functional magnetic resonance imaging (fMRI), network dynamics, presymptomatic, DISEASE, Cellular and Molecular Neuroscience, Developmental Neuroscience, SDG 3 - Good Health and Well-being, Humans, Cognitive Dysfunction, ddc:610, BRAIN, BATTERY, Science & Technology, Health Policy, Brain, FUNCTIONAL CONNECTIVITY, Magnetic Resonance Imaging, STATE, TIME, Psychiatry and Mental health, COMPENSATION, Frontotemporal Dementia, Mutation, FEATURED ARTICLES, Neurology (clinical), Human medicine, Neurosciences & Neurology, Geriatrics and Gerontology, Life Sciences & Biomedicine
Abstract: © 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., Introduction: We tested whether changes in functional networks predict cognitive decline and conversion from the presymptomatic prodrome to symptomatic disease in familial frontotemporal dementia (FTD). Methods: For hypothesis generation, 36 participants with behavioral variant FTD (bvFTD) and 34 controls were recruited from one site. For hypothesis testing, we studied 198 symptomatic FTD mutation carriers, 341 presymptomatic mutation carriers, and 329 family members without mutations. We compared functional network dynamics between groups, with clinical severity and with longitudinal clinical progression. Results: We identified a characteristic pattern of dynamic network changes in FTD, which correlated with neuropsychological impairment. Among presymptomatic mutation carriers, this pattern of network dynamics was found to a greater extent in those who subsequently converted to the symptomatic phase. Baseline network dynamic changes predicted future cognitive decline in symptomatic participants and older presymptomatic participants. Discussion: Dynamic network abnormalities in FTD predict cognitive decline and symptomatic conversion. Highlights: We investigated brain network predictors of dementia symptom onset Frontotemporal dementia results in characteristic dynamic network patterns Alterations in network dynamics are associated with neuropsychological impairment Network dynamic changes predict symptomatic conversion in presymptomatic carriers Network dynamic changes are associated with longitudinal cognitive decline., GENFI was funded by the Medical Research Council UK (MR/M023664/1), the Bluefield Project, the JPND GENFI-PROX grant (by DLR/BMBF 2019-02248) and by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198). The study was co-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge (BRC-1215-20014), the Cambridge Centre for Parkinson-plus (RG95450); the Wellcome Trust (220258); the Evelyn Trust (17/09) and Medical Research Council (SUAG/092 116768).
Published: 2022

38. Examining empathy deficits across familial forms of frontotemporal dementia within the GENFI cohort

Author: Foster, Phoebe H, Russell, Lucy L, Moreno, Fermin, Meeter, Lieke, Miltenberger, Gabriel, van Minkelen, Rick, Mitchell, Sara, Moore, Katrina, Nacmias, Benedetta, Nelson, Annabel, Öijerstedt, Linn, Olives, Jaume, Ourselin, Sebastien, Sanchez-Valle, Raquel, Padovani, Alessandro, Panman, Jessica, Papma, Janne M, Pijnenburg, Yolande, Polito, Cristina, Premi, Enrico, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Laforce, Robert, Rinaldi, Daisy, Rittman, Tim, Rogaeva, Ekaterina, Rollin, Adeline, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Saracino, Dario, Sayah, Sabrina, Graff, Caroline, Scarpini, Elio, Schönecker, Sonja, Seelaar, Harro, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Swift, Imogen, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Masellis, Mario, Tang-Wai, David, Thomas, David L, Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Todd, Emily, Van Damme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Tartaglia, Carmela, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Rowe, James B, Borroni, Barbara, Finger, Elizabeth, Synofzik, Matthis, Peakman, Georgia, Galimberti, Daniela, Vandenberghe, Rik, de Mendonça, Alexandre, Butler, Chris R, Gerhard, Alex, Ducharme, Simon, Le Ber, Isabelle, Tagliavini, Fabrizio, Santana, Isabel, Pasquier, Florence, Convery, Rhian S, Levin, Johannes, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Rohrer, Jonathan D, Initiative, Genetic FTD, Afonso, Sónia, Almeida, Maria Rosario, Anderl-Straub, Sarah, Andersson, Christin, Bouzigues, Arabella, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Bertoux, Maxime, Greaves, Caroline V, Bertrand, Anne, Bessi, Valentina, Black, Sandra, Borrego-Ecija, Sergi, Bras, Jose, Brice, Alexis, Bruffaerts, Rose, Camuzat, Agnès, Cañada, Marta, Cantoni, Valentina, Bocchetta, Martina, Caroppo, Paola, Cash, David, Castelo-Branco, Miguel, Colliot, Olivier, Cope, Thomas, Deramecourt, Vincent, de Arriba, María, Di Fede, Giuseppe, Díez, Alina, Duro, Diana, Cash, David M, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B, Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Funkiewiez, Aurélie, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, van Swieten, John C, Gazzina, Stefano, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Karnath, Hans Otto, Jiskoot, Lize C, Keren, Ron, Kuchcinski, Gregory, Langheinrich, Tobias, Lebouvier, Thibaud, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Rowe, James [0000-0001-7216-8679], Apollo - University of Cambridge Repository, Neurology, Amsterdam Neuroscience - Neurodegeneration, and Repositório da Universidade de Lisboa
Subjects: Empathic concern, Cognitive Neuroscience, Medizin, Empathy, Frontotemporal dementia, Interpersonal Reactivity Index, Perspective taking, C9orf72 Protein, Humans, Mutation, Progranulins, tau Proteins, Frontotemporal Dementia, Pick Disease of the Brain, Experimental and Cognitive Psychology, genetics [Progranulins], diagnosis [Frontotemporal Dementia], mental disorders, ddc:610, genetics [C9orf72 Protein], genetics [Frontotemporal Dementia], genetics [tau Proteins], Neuropsychology and Physiological Psychology
Abstract: © 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/)., Background: Reduced empathy is a common symptom in frontotemporal dementia (FTD). Although empathy deficits have been extensively researched in sporadic cases, few studies have explored the differences in familial forms of FTD. Methods: Empathy was examined using a modified version of the Interpersonal Reactivity Index (mIRI) in 676 participants from the Genetic FTD Initiative: 216 mutation-negative controls, 192 C9orf72 expansion carriers, 193 GRN mutation carriers and 75 MAPT mutation carriers. Using global scores from the CDR® plus NACC FTLD, mutation carriers were divided into three groups, asymptomatic (0), very mildly symptomatic/prodromal (.5), or fully symptomatic (1 or more). The mIRI Total score, as well as the subscores of Empathic Concern (EC) and Perspective Taking (PT) were assessed. Linear regression models with bootstrapping were used to assess empathy ratings across genetic groups, as well as across phenotypes in the symptomatic carriers. Neural correlates of empathy deficits were examined using a voxel-based morphometry (VBM) analysis. Results: All fully symptomatic groups scored lower on the mIRI Total, EC, and PT when compared to controls and their asymptomatic or prodromal counterparts (all p < .001). Prodromal C9orf72 expansion carriers also scored significantly lower than controls on the mIRI Total score (p = .046). In the phenotype analysis, all groups (behavioural variant FTD, primary progressive aphasia and FTD with amyotrophic lateral sclerosis) scored significantly lower than controls (all p < .007). VBM revealed an overlapping neural correlate of the mIRI Total score across genetic groups in the orbitofrontal lobe but with additional involvement in the temporal lobe, insula and basal ganglia in both the GRN and MAPT groups, and uniquely more posterior regions such as the parietal lobe and thalamus in the GRN group, and medial temporal structures in the MAPT group. Conclusions: Significant empathy deficits present in genetic FTD, particularly in symptomatic individuals and those with a bvFTD phenotype, while prodromal deficits are only seen using the mIRI in C9orf72 expansion carriers., This work was supported by the NIHR UCL/H Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. JDR is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Bluefield Project and the JPND GENFI-PROX grant (2019-02248). Several authors of this publication are members of the European Reference Network for Rare Neurological Diseases - Project ID No 739510. RC/CG are supported by a Frontotemporal Dementia Research Studentships in Memory of David Blechner funded through The National Brain Appeal (RCN 290173). MB is supported by a Fellowship award from the Alzheimer's Society, UK (AS-JF-19a-004-517). MB's work is also supported by the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. JCVS was supported by the Dioraphte Foundation grant 09-02-03-00, the Association for Frontotemporal Dementias Research Grant 2009, The Netherlands Organisation for Scientific Research grant HCMI 056-13-018, ZonMw Memorabel (Deltaplan Dementie, project number 733 051 042), Alzheimer Nederland and the Bluefield project. FM received funding from the Tau Consortium and the Center for Networked Biomedical Research on Neurodegenerative Disease (CIBERNED). RS-V is supported by an Alzheimer’s Research UK Clinical Research Training Fellowship (ARUK-CRF2017B-2), and has received funding from Fundació Marató de TV3, Spain (grant no. 20143810). CG received funding from JPND-Prefrontals VR Dnr 529-2014-7504, VR 2015-02926 and 2018-02754, the Swedish FTD Inititative-Schörling Foundation, Alzheimer Foundation, Brain Foundation and Stockholm County Council ALF. MM has received funding from a Canadian Institute of Health Research operating grant and the Weston Brain Institute and Ontario Brain Institute. JBR has received funding from the Wellcome Trust (103838) and is supported by the Cambridge University Centre for Frontotemporal Dementia, the Medical Research Council (SUAG/051 G101400) and the National Institute for Health Research Cambridge Biomedical Research Centre (BRC-1215-20014). EF has received funding from a CIHR grant #327387. DG received support from the EU Joint Programme – Neurodegenerative Disease Research and the Italian Ministry of Health (PreFrontALS) grant 733051042. RV has received funding from the Mady Browaeys Fund for Research into Frontotemporal Dementia. MO has received funding from BMBF (FTLDc).
Published: 2022

39. Plasma progranulin levels for frontotemporal dementia in clinical practice: a 10-year French experience

Author: Sellami, Leila, Rucheton, Benoît, Ben Younes, Imen, Camuzat, Agnès, Saracino, Dario, Rinaldi, Daisy, Epelbaum, Stephane, Azuar, Carole, Levy, Richard, Auriacombe, Sophie, Hannequin, Didier, Pariente, Jérémie, Barbier, Mathieu, Boutoleau-Bretonnière, Claire, Couratier, Philippe, Pasquier, Florence, Deramecourt, Vincent, Sauvée, Mathilde, Sarazin, Marie, Lagarde, Julien, Roué-Jagot, Carole, Forlani, Sylvie, Jornea, Ludmila, David, Isabelle, LeGuern, Eric, Dubois, Bruno, Brice, Alexis, Clot, Fabienne, Lamari, Foudil, and Le Ber, Isabelle
Published: 2020
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40. Anomia is present pre-symptomatically in frontotemporal dementia due to MAPT mutations

Author: Bouzigues, Arabella, Russell, Lucy L, Tiraboschi, Pietro, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B, Miltenberger, Gabriel, Masellis, Mario, do Couto, Frederico Simões, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Tartaglia, Maria Carmela, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Finger, Elizabeth, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, van Swieten, John C, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Seelaar, Harro, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Engel, Annerose, Polyakova, Maryna, Jiskoot, Lize, Sorbi, Sandro, Butler, Chris R, Graff, Caroline, Peakman, Georgia, Gerhard, Alexander, Langheinrich, Tobias, Laforce, Robert, Sanchez-Valle, Raquel, de Mendonça, Alexandre, Moreno, Fermin, Synofzik, Matthis, Vandenberghe, Rik, Ducharme, Simon, Le Ber, Isabelle, Bocchetta, Martina, Levin, Johannes, Danek, Adrian, Otto, Markus, Pasquier, Florence, Santana, Isabel, Rohrer, Jonathan D, Genetic FTD Initiative, GENFI, Esteve, Aitana Sogorb, Nelson, Annabel, Greaves, Caroline V, Heller, Carolin, Cash, David, Thomas, David L, Todd, Emily, Benotmane, Hanya, Zetterberg, Henrik, Swift, Imogen J, Nicholas, Jennifer, Samra, Kiran, Convery, Rhian S, Shafei, Rachelle, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Rowe, James B, Caroppo, Paola, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Keren, Ron, Black, Sandra, Mitchell, Sara, Borroni, Barbara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Papma, Janne M, Giannini, Lucia, Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Galimberti, Daniela, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Bouzigues, Arabella [0000-0002-0267-8590], Russell, Lucy L [0000-0001-5023-5893], Peakman, Georgia [0000-0002-3319-138X], Bocchetta, Martina [0000-0003-1814-5024], Greaves, Caroline V [0000-0002-6446-1960], Convery, Rhian S [0000-0002-9477-1812], Rowe, James B [0000-0001-7216-8679], Finger, Elizabeth [0000-0003-4461-7427], van Swieten, John C [0000-0001-6278-6844], Levin, Johannes [0000-0001-5092-4306], Otto, Markus [0000-0002-6647-5944], Apollo - University of Cambridge Repository, Esteve, Aitana Sogorb (Beitragende*r), Nelson, Annabel (Beitragende*r), Heller, Carolin (Beitragende*r), Cash, David (Beitragende*r), Thomas, David L (Beitragende*r), Benotmane, Hanya (Beitragende*r), Zetterberg, Henrik (Beitragende*r), Swift, Imogen J (Beitragende*r), Nicholas, Jennifer (Beitragende*r), Samra, Kiran (Beitragende*r), Shafei, Rachelle (Beitragende*r), Timberlake, Carolyn (Beitragende*r), Cope, Thomas (Beitragende*r), Rittman, Timothy (Beitragende*r), Benussi, Alberto (Beitragende*r), Premi, Enrico (Beitragende*r), Gasparotti, Roberto (Beitragende*r), Archetti, Silvana (Beitragende*r), Gazzina, Stefano (Beitragende*r), Cantoni, Valentina (Beitragende*r), Arighi, Andrea (Beitragende*r), Fenoglio, Chiara (Beitragende*r), Scarpini, Elio (Beitragende*r), Fumagalli, Giorgio (Beitragende*r), Borracci, Vittoria (Beitragende*r), Rossi, Giacomina (Beitragende*r), Giaccone, Giorgio (Beitragende*r), Caroppo, Paola (Beitragende*r), Prioni, Sara (Beitragende*r), Redaelli, Veronica (Beitragende*r), Tang-Wai, David (Beitragende*r), Rogaeva, Ekaterina (Beitragende*r), Castelo-Branco, Miguel (Beitragende*r), Keren, Ron (Beitragende*r), Black, Sandra (Beitragende*r), Mitchell, Sara (Beitragende*r), Shoesmith, Christen (Beitragende*r), Bartha, Robart (Beitragende*r), Rademakers, Rosa (Beitragende*r), Poos, Jackie (Beitragende*r), Papma, Janne M (Beitragende*r), Giannini, Lucia (Beitragende*r), Minkelen, Rick (Beitragende*r), Pijnenburg, Yolande (Beitragende*r), Nacmias, Benedetta (Beitragende*r), Ferrari, Camilla (Beitragende*r), Polito, Cristina (Beitragende*r), Lombardi, Gemma (Beitragende*r), Bessi, Valentina (Beitragende*r), Veldsman, Michele (Beitragende*r), Andersson, Christin (Beitragende*r), Thonberg, Hakan (Beitragende*r), Öijerstedt, Linn (Beitragende*r), Jelic, Vesna (Beitragende*r), Thompson, Paul (Beitragende*r), Lladó, Albert (Beitragende*r), Antonell, Anna (Beitragende*r), Olives, Jaume (Beitragende*r), Balasa, Mircea (Beitragende*r), Bargalló, Nuria (Beitragende*r), Borrego-Ecija, Sergi (Beitragende*r), Verdelho, Ana (Beitragende*r), Maruta, Carolina (Beitragende*r), Ferreira, Catarina B (Beitragende*r), Miltenberger, Gabriel (Beitragende*r), do Couto, Frederico Simões (Beitragende*r), Gabilondo, Alazne (Beitragende*r), Gorostidi, Ana (Beitragende*r), Villanua, Jorge (Beitragende*r), Cañada, Marta (Beitragende*r), Tainta, Mikel (Beitragende*r), Zulaica, Miren (Beitragende*r), Barandiaran, Myriam (Beitragende*r), Alves, Patricia (Beitragende*r), Bender, Benjamin (Beitragende*r), Wilke, Carlo (Beitragende*r), Graf, Lisa (Beitragende*r), Vogels, Annick (Beitragende*r), Vandenbulcke, Mathieu (Beitragende*r), Van Damme, Philip (Beitragende*r), Bruffaerts, Rose (Beitragende*r), Poesen, Koen (Beitragende*r), Rosa-Neto, Pedro (Beitragende*r), Gauthier, Serge (Beitragende*r), Camuzat, Agnès (Beitragende*r), Brice, Alexis (Beitragende*r), Bertrand, Anne (Beitragende*r), Funkiewiez, Aurélie (Beitragende*r), Rinaldi, Daisy (Beitragende*r), Saracino, Dario (Beitragende*r), Colliot, Olivier (Beitragende*r), Sayah, Sabrina (Beitragende*r), Prix, Catharina (Beitragende*r), Wlasich, Elisabeth (Beitragende*r), Wagemann, Olivia (Beitragende*r), Loosli, Sandra (Beitragende*r), Schönecker, Sonja (Beitragende*r), Hoegen, Tobias (Beitragende*r), Lombardi, Jolina (Beitragende*r), Anderl-Straub, Sarah (Beitragende*r), Rollin, Adeline (Beitragende*r), Kuchcinski, Gregory (Beitragende*r), Bertoux, Maxime (Beitragende*r), Lebouvier, Thibaud (Beitragende*r), Deramecourt, Vincent (Beitragende*r), Santiago, Beatriz (Beitragende*r), Duro, Diana (Beitragende*r), Leitão, Maria João (Beitragende*r), Almeida, Maria Rosario (Beitragende*r), Tábuas-Pereira, Miguel (Beitragende*r), Afonso, Sónia (Beitragende*r), Engel, Annerose (Beitragende*r), Polyakova, Maryna (Beitragende*r), Repositório da Universidade de Lisboa, Genetic FTD Initiative, GENFI, and Neurology
Subjects: Progranulin, Clinical Neurology, Medizin, Anomia, tau Proteins, Naming, IMPAIRMENTS, VARIANTS, diagnostic imaging [Frontotemporal Dementia], genetics [Progranulins], Cognition, Progranulins, Settore BIO/13 - Biologia Applicata, complications [Frontotemporal Dementia], mental disorders, C9orf72, Humans, ddc:610, genetics [C9orf72 Protein], genetics [Frontotemporal Dementia], Biology, Science & Technology, C9orf72 Protein, MORPHOMETRIC ANALYSES, ANATOMY, ALZHEIMERS-DISEASE, genetics [tau Proteins], Neurology, Frontotemporal Dementia, Mutation, PATTERNS, Frontotemporal dementia, Tau, Human medicine, Neurosciences & Neurology, Neurology (clinical), complications [Anomia], Life Sciences & Biomedicine, MRI
Abstract: Funder: Alzheimer’s Research UK; doi: http://dx.doi.org/10.13039/501100002283, Funder: UCLH Biomedical Research Centre; doi: http://dx.doi.org/10.13039/501100012317, Funder: Medical Research Council; doi: http://dx.doi.org/10.13039/501100000265, Funder: Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, Funder: Bluefield Project, INTRODUCTION: A third of frontotemporal dementia (FTD) is caused by an autosomal-dominant genetic mutation in one of three genes: microtubule-associated protein tau (MAPT), chromosome 9 open reading frame 72 (C9orf72) and progranulin (GRN). Prior studies of prodromal FTD have identified impaired executive function and social cognition early in the disease but few have studied naming in detail. METHODS: We investigated performance on the Boston Naming Test (BNT) in the GENetic Frontotemporal dementia Initiative cohort of 499 mutation carriers and 248 mutation-negative controls divided across three genetic groups: C9orf72, MAPT and GRN. Mutation carriers were further divided into 3 groups according to their global CDR plus NACC FTLD score: 0 (asymptomatic), 0.5 (prodromal) and 1 + (fully symptomatic). Groups were compared using a bootstrapped linear regression model, adjusting for age, sex, language and education. Finally, we identified neural correlates of anomia within carriers of each genetic group using a voxel-based morphometry analysis. RESULTS: All symptomatic groups performed worse on the BNT than controls with the MAPT symptomatic group scoring the worst. Furthermore, MAPT asymptomatic and prodromal groups performed significantly worse than controls. Correlates of anomia in MAPT mutation carriers included bilateral anterior temporal lobe regions and the anterior insula. Similar bilateral anterior temporal lobe involvement was seen in C9orf72 mutation carriers as well as more widespread left frontal atrophy. In GRN mutation carriers, neural correlates were limited to the left hemisphere, and involved frontal, temporal, insula and striatal regions. CONCLUSION: This study suggests the development of early anomia in MAPT mutation carriers, likely to be associated with impaired semantic knowledge. Clinical trials focused on the prodromal period within individuals with MAPT mutations should use language tasks, such as the BNT for patient stratification and as outcome measures.
Published: 2022

41. Factors influencing the age at onset in familial frontotemporal lobar dementia: Important weight of genetics

Author: Barbier, Mathieu, Camuzat, Agnès, Houot, Marion, Clot, Fabienne, Caroppo, Paola, Fournier, Clémence, Rinaldi, Daisy, Pasquier, Florence, Hannequin, Didier, Pariente, Jérémie, Larcher, Kathy, Brice, Alexis, Génin, Emmanuelle, Sabbagh, Audrey, and Le Ber, Isabelle
Published: 2017
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42. Cognitive composites for genetic frontotemporal dementia: GENFI-Cog

Author: Poos, Jackie M, Moore, Katrina M, Seelaar, Harro, Vandamme, Philip, Vandenbulcke, Mathieu, Ferreira, Catarina B, Miltenberger, Gabriel, Maruta, Carolina, Verdelho, Ana, Afonso, Sónia, Taipa, Ricardo, Caroppo, Paola, Di Fede, Giuseppe, Pijnenburg, Yolande A L, Giaccone, Giorgio, Prioni, Sara, Redaelli, Veronica, Rossi, Giacomina, Duro, Diana, Almeida, Maria Rosario, Castelo-Branco, Miguel, Leitão, Maria João, Tabuas-Pereira, Miguel, Santiago, Beatriz, Moreno, Fermin, Gauthier, Serge, Rosa-Neto, Pedro, Veldsman, Michele, Thompson, Paul, Langheinrich, Tobias, Prix, Catharina, Hoegen, Tobias, Wlasich, Elisabeth, Loosli, Sandra, Schonecker, Sonja, Sanchez-Valle, Raquel, Anderl-Straub, Sarah, Lombardi, Jolina, Bargalló, Nuria, Benussi, Alberto, Cantoni, Valentina, Bertoux, Maxime, Bertrand, Anne, Brice, Alexis, Camuzat, Agnès, Colliot, Olivier, Borroni, Barbara, Sayah, Sabrina, Funkiewiez, Aurélie, Rinaldi, Daisy, Lombardi, Gemma, Nacmias, Benedetta, Saracino, Dario, Bessi, Valentina, Ferrari, Camilla, Cañada, Marta, Deramecourt, Vincent, Laforce, Robert, Kuchcinski, Gregory, Lebouvier, Thibaud, Ourselin, Sebastien, Polito, Cristina, Rollin, Adeline, Masellis, Mario, Tartaglia, Carmela, Graff, Caroline, Galimberti, Daniela, Nicholas, Jennifer, Rowe, James B, Finger, Elizabeth, Synofzik, Matthis, Vandenberghe, Rik, de Mendonça, Alexandre, Tiraboschi, Pietro, Santana, Isabel, Ducharme, Simon, Butler, Chris, Gerhard, Alexander, Russell, Lucy L, Levin, Johannes, Danek, Adrian, Otto, Markus, Le Ber, Isabel, Pasquier, Florence, van Swieten, John C, Rohrer, Jonathan D, Initiative, Genetic FTD, Bouzigues, Arabella, Rossor, Martin N, Peakman, Georgia, Fox, Nick C, Warren, Jason D, Bocchetta, Martina, Swift, Imogen J, Shafei, Rachelle, Heller, Carolin, Todd, Emily, Cash, David, Woollacott, Ione, Zetterberg, Henrik, Convery, Rhian S, Nelson, Annabel, Guerreiro, Rita, Bras, Jose, Thomas, David L, Mead, Simon, Meeter, Lieke, Panman, Jessica, van Minkelen, Rick, Barandiaran, Myriam, Indakoetxea, Begoña, Jiskoot, Lize C, Gabilondo, Alazne, Tainta, Mikel, Gorostidi, Ana, Zulaica, Miren, Díez, Alina, Villanua, Jorge, Borrego-Ecija, Sergi, Olives, Jaume, Lladó, Albert, Balasa, Mircea, van der Ende, Emma, Antonell, Anna, Bargallo, Nuria, Premi, Enrico, Gazzina, Stefano, Gasparotti, Roberto, Archetti, Silvana, Black, Sandra, Mitchell, Sara, Rogaeva, Ekaterina, Freedman, Morris, van den Berg, Esther, Keren, Ron, Tang-Wai, David, Thonberg, Hakan, Öijerstedt, Linn, Andersson, Christin, Jelic, Vesna, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Papma, Janne M, Cope, Thomas, Timberlake, Carolyn, Rittman, Timothy, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Wilke, Carlo, Karnarth, Hans-Otto, Bender, Benjamin, Bruffaerts, Rose, Neurology, Amsterdam Neuroscience - Neurodegeneration, Medical Research Council, Clinical Genetics, Rowe, James [0000-0001-7216-8679], Rohrer, Jonathan D [0000-0002-6155-8417], and Apollo - University of Cambridge Repository
Subjects: PROGRESSION, Neuropsychological Tests, Composite score, Genetic FTD Initiative (GENFI), diagnosis [Frontotemporal Dementia], Cognition, CRITERIA, Attention, genetics [Frontotemporal Dementia], 11 Medical and Health Sciences, Language, Executive function, Frontotemporal dementia, Memory, Neuropsychology, Social cognition, Humans, Mutation, Prodromal Symptoms, Sample Size, tau Proteins, Frontotemporal Dementia, CARRIERS, Neurology, Psychology, Life Sciences & Biomedicine, CLINICAL-TRIALS, RC321-571, medicine.medical_specialty, Cognitive Neuroscience, Clinical Neurology, genetics [Mutation], Neurosciences. Biological psychiatry. Neuropsychiatry, Physical medicine and rehabilitation, Cog, mental disorders, medicine, ddc:610, RC346-429, Science & Technology, Research, Neurosciences, medicine.disease, genetics [tau Proteins], Neurosciences & Neurology, Neurology (clinical), Neurology. Diseases of the nervous system
Abstract: Funder: Alzheimer's Research UK, Funder: Alzheimer's Society, Funder: Brain Research UK, Funder: the Wolfson Foundation, Funder: NIHR UCL/H Biomedical Research Centre, Funder: Leonard Wolfson Experimental Neurology Centre Clinical Research Facility, Funder: UK Dementia Research Institute, Funder: UK Medical Research Council, Funder: Bluefield project, Funder: the Association for Frontotemporal Dementias Research Grant 2009, BACKGROUND: Clinical endpoints for upcoming therapeutic trials in frontotemporal dementia (FTD) are increasingly urgent. Cognitive composite scores are often used as endpoints but are lacking in genetic FTD. We aimed to create cognitive composite scores for genetic frontotemporal dementia (FTD) as well as recommendations for recruitment and duration in clinical trial design. METHODS: A standardized neuropsychological test battery covering six cognitive domains was completed by 69 C9orf72, 41 GRN, and 28 MAPT mutation carriers with CDR�� plus NACC-FTLD �� 0.5 and 275 controls. Logistic regression was used to identify the combination of tests that distinguished best between each mutation carrier group and controls. The composite scores were calculated from the weighted averages of test scores in the models based on the regression coefficients. Sample size estimates were calculated for individual cognitive tests and composites in a theoretical trial aimed at preventing progression from a prodromal stage (CDR�� plus NACC-FTLD 0.5) to a fully symptomatic stage (CDR�� plus NACC-FTLD �� 1). Time-to-event analysis was performed to determine how quickly mutation carriers progressed from CDR�� plus NACC-FTLD = 0.5 to �� 1 (and therefore how long a trial would need to be). RESULTS: The results from the logistic regression analyses resulted in different composite scores for each mutation carrier group (i.e. C9orf72, GRN, and MAPT). The estimated sample size to detect a treatment effect was lower for composite scores than for most individual tests. A Kaplan-Meier curve showed that after 3 years, ~ 50% of individuals had converted from CDR�� plus NACC-FTLD 0.5 to �� 1, which means that the estimated effect size needs to be halved in sample size calculations as only half of the mutation carriers would be expected to progress from CDR�� plus NACC FTLD 0.5 to �� 1 without treatment over that time period. DISCUSSION: We created gene-specific cognitive composite scores for C9orf72, GRN, and MAPT mutation carriers, which resulted in substantially lower estimated sample sizes to detect a treatment effect than the individual cognitive tests. The GENFI-Cog composites have potential as cognitive endpoints for upcoming clinical trials. The results from this study provide recommendations for estimating sample size and trial duration.
Published: 2022

43. Disease Progression Score Estimation From Multimodal Imaging and MicroRNA Data Using Supervised Variational Autoencoders

Author: Kmetzsch, Virgilio, primary, Becker, Emmanuelle, additional, Saracino, Dario, additional, Rinaldi, Daisy, additional, Camuzat, Agnes, additional, Le Ber, Isabelle, additional, and Colliot, Olivier, additional
Published: 2022
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44. Building bridges for innovation in ageing: Synergies between action groups of the EIP on AHA

Author: Bousquet, Jean, Bewick, M., Cano, A., Eklund, P., Fico, G., Goswami, N., Guldemond, N. A., Henderson, D., Hinkema, M. J., Liotta, G., Mair, A., Molloy, W., Monaco, A., Monsonis-Paya, I., Nizinska, A., Papadopoulos, H., Pavlickova, A., Pecorelli, S., Prados-Torres, A., Roller-Wirnsberger, R. E., Somekh, D., Vera-Muñoz, C., Visser, F., Farrell, J., Malva, J., Andersen Ranberg, K., Camuzat, T., Carriazo, A. M., Crooks, G., Gutter, Z., Iaccarino, G., de Keenoy, E. Manuel, Moda, G., Rodriguez-Mañas, L., Vontetsianos, T., Abreu, C., Alonso, J., Alonso-Bouzon, C., Ankri, J., Arredondo, M. T., Avolio, F., Bedbrook, A., Białoszewski, A. Z., Blain, H., Bourret, R., Cabrera-Umpierrez, M. F., Catala, A., O’Caoimh, R., Cesari, M., Chavannes, N. H., Correia-Da-Sousa, J., Dedeu, T., Ferrando, M., Ferri, M., Fokkens, W. J., Garcia-Lizana, F., Guérin, O., Hellings, P. W., Haahtela, T., Illario, M., Inzerilli, M. C., Lodrup Carlsen, K. C., Kardas, P., Keil, T., Maggio, M., Mendez-Zorrilla, A., Menditto, E., Mercier, J., Michel, J. P., Murray, R., Nogues, M., O’Byrne-Maguire, I., Pappa, D., Parent, A. S., Pastorino, M., Robalo-Cordeiro, C., Samolinski, B., Siciliano, P., Teixeira, A. M., Tsartara, S. I., Valiulis, A., Vandenplas, O., Vasankari, T., Vellas, B., Vollenbroek-Hutten, M., Wickman, M., Yorgancioglu, A., Zuberbier, T., Barbagallo, M., Canonica, G. W., Klimek, L., Maggi, S., Aberer, W., Akdis, C., Adcock, I. M., Agache, I., Albera, C., Alonso-Trujillo, F., Angel Guarcia, M., Annesi-Maesano, I., Apostolo, J., Arshad, S. H., Attalin, V., Avignon, A., Bachert, C., Baroni, I., Bel, E., Benson, M., Bescos, C., Blasi, F., Barbara, C., Bergmann, K. C., Bernard, P. L., Bonini, S., Bousquet, P. J., Branchini, B., Brightling, C. E., Bruguière, V., Bunu, C., Bush, A., Caimmi, D. P., Calderon, M. A., Canovas, G., Cardona, V., Carlsen, K. H., Cesario, A., Chkhartishvili, E., Chiron, R., Chivato, T., Chung, K. F., D’Angelantonio, M., de Carlo, G., Cholley, D., Chorin, F., Combe, B., Compas, B., Costa, D. J., Costa, E., Coste, O., Coupet, A. -L., Crepaldi, G., Custovic, A., Dahl, R., Dahlen, S. E., Demoly, P., Devillier, P., Didier, A., Dinh-Xuan, A. T., Djukanovic, R., Dokic, D., du Toit, G., Dubakiene, R., Dupeyron, A., Emuzyte, R., Fiocchi, A., Wagner, A., Fletcher, M., Fonseca, J., Fougère, B., Gamkrelidze, A., Garces, G., Garcia-Aymeric, J., Garcia-Zapirain, B., Gemicioğlu, B., Gouder, C., Hellquist-Dahl, B., Hermosilla-Gimeno, I., Héve, D., Holland, C., Humbert, M., Hyland, M., Johnston, S. L., Just, J., Jutel, M., Kaidashev, I. P., Kaitov, M., Kalayci, O., Kalyoncu, A. F., Keijser, W., Kerstjens, H., Knezović, J., Kowalski, M., Koppelman, G. H., Kotska, T., Kovac, M., Kull, I., Kuna, P., Kvedariene, V., Lepore, V., Macnee, W., Maggio, M., Magnan, A., Majer, I., Manning, P., Marcucci, M., Marti, T., Masoli, M., Melen, E., Miculinic, N., Mihaltan, F., Milenkovic, B., Millot-Keurinck, J., Mlinarić, H., Momas, I., Montefort, S., Morais-Almeida, M., Moreno-Casbas, T., Mösges, R., Mullol, J., Nadif, R., Nalin, M., Navarro-Pardo, E., Nekam, K., Ninot, G., Paccard, D., Pais, S., Palummeri, E., Panzner, P., Papadopoulos, N. K., Papanikolaou, C., Passalacqua, G., Pastor, E., Perrot, M., Plavec, D., Popov, T. A., Postma, D. S., Price, D., Raffort, N., Reuzeau, J. C., Robine, J. M., Rodenas, F., Robusto, F., Roche, N., Romano, A., Romano, V., Rosado-Pinto, J., Roubille, F., Ruiz, F., Ryan, D., Salcedo, T., Schmid-Grendelmeier, P., Schulz, H., Schunemann, H. J., Serrano, E., Sheikh, A., Shields, M., Siafakas, N., Scichilone, N., Siciliano, P., Skrindo, I., Smit, H. A., Sourdet, S., Sousa-Costa, E., Spranger, O., Sooronbaev, T., Sruk, V., Sterk, P. J., Todo-Bom, A., Touchon, J., Tramontano, D., Triggiani, M., Tsartara, S. I., Valero, A. L., Valovirta, E., van Ganse, E., van Hage, M., van den Berge, M., Vandenplas, O., Ventura, M. T., Vergara, I., Vezzani, G., Vidal, D., Viegi, G., Wagemann, M., Whalley, B., Wickman, M., Wilson, N., Yiallouros, P. K., Žagar, M., Zaidi, A., Zidarn, M., Hoogerwerf, E. J., Usero, J., Zuffada, R., Senn, A., and de Oliveira-Alves, B.
Published: 2017
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45. Primary progressive aphasias associated with C9orf72 expansions: Another side of the story

Author: idier Hannequin, Eino Solje, Sabrina Sayah, Emmanuel Gerardin, Marie Sarazin, Florence Pasquier, Marion Houot, Assi-Hervé Oya, Martine Vercelletto, Julien Lagarde, Marie Noguès-Lassiaille, Marie Chupin, Vincent Deramecourt, Sophie Auriacombe, Agnès Camuzat, Marc Teichmann, Jérémie Pariente, Sophie Ferrieux, Lucette Lacomblez, Mathieu Chastan, Jacques Monteil, Yaohua Chen, Marie-Paule Boncoeur, Lorenzo Cipriano, Anne Bissery, Simona Bottani, David Wallon, Christine Delmaire, Carole Roué-Jagot, Benjamin Le Toullec, Bernard-François Michel, Grégory Petyt, Olivier Martinaud, Philippe Couratier, Dario Saracino, Adeline Rollin-Sillaire, Daisy Rinaldi, Mira Didic, Serge Belliard, Amandine Géraudie, Géraldine Lautrette, Frédérique Etcharry-Bouyx, Xavier Delbeuck, Richard Levy, Frédéric Blanc, Mathieu Ceccaldi, Christel Thauvin-Robinet, Marie-Odile Habert, Eve Benchetrit, Maïté Formaglio, Alexis Brice, Isabelle Le Ber, Charles Duyckaerts, Véronique Golfier, Raffaella Migliaccio, Marie-Anne Mackowiak, Catherine Thomas-Antérion, Anne Bertrand, Olivier Colliot, François Sellal, Claire Boutoleau-Bretonnière, Anne M. Remes, Hugo Bertin, Aurélie Funkiewiez, and Stéphanie Bombois
Subjects: medicine.medical_specialty, C9orf72 Protein, Apraxias, Cognitive Neuroscience, Inferior frontal gyrus, Experimental and Cognitive Psychology, Frontotemporal lobar degeneration, respiratory system, Audiology, medicine.disease, Magnetic Resonance Imaging, Apraxia, Primary progressive aphasia, Aphasia, Primary Progressive, Neuropsychology and Physiological Psychology, Atrophy, C9orf72, medicine, Humans, Speech, Orbitofrontal cortex, Psychology, Language, Frontotemporal dementia
Abstract: C9orf72 repeat expansions are rarely associated with primary progressive aphasias (PPA). In-depth characterization of the linguistic deficits, and the underlying patterns of grey-matter atrophy in PPA associated with the C9orf72 expansions (PPA-C9orf72) are currently lacking. In this study, we comprehensively analyzed a unique series of 16 patients affected by PPA-C9orf72. Eleven patients were issued from two independent French and Finnish cohorts, and five were identified by means of literature review. Voxel-based morphometry (VBM) studies were performed on three of them. This study depicts the spectrum of C9orf72–related aphasic phenotypes, and illustrates their linguistic presentation. The non-fluent/agrammatic variant was the most frequent phenotype in our series (9/16 patients, 56%), with apraxia of speech being the main defining feature. Left frontal lobe atrophy was present in these subjects, peaking in inferior frontal gyrus. Three patients (19%) showed the semantic variant, with progression of atrophy in temporo-polar regions, later involving orbitofrontal cortex. Anterior temporal lobe dysfunction was also particularly relevant in two patients (12.5%) with mixed forms of PPA. Lastly, two patients (12.5%) had unclassifiable PPA with predominating word-finding difficulties. No PPA-C9orf72 patients in our series fulfilled the criteria of the logopenic variant. Importantly, this study underlines the role of C9orf72 mutation in the disruption of the most anterior parts of the language network, including prefrontal and temporo-polar areas. It provides guidelines for C9orf72 testing in PPA patients, with important clinical impact as gene-specific therapies are upcoming.
Published: 2021

46. Differential impairment of cerebrospinal fluid synaptic biomarkers in the genetic forms of frontotemporal dementia

Author: Sogorb-Esteve, Aitana, Nilsson, Johanna, Borroni, Barbara, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, de Mendonça, Alexandre, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B, Miltenberger, Gabriel, do Couto, Frederico Simões, Gabilondo, Alazne, Galimberti, Daniela, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Sanchez-Valle, Raquel, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Laforce, Robert, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Moreno, Fermin, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Synofzik, Matthis, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Graff, Caroline, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B, Swift, Imogen J, Vandenberghe, Rik, Finger, Elizabeth, Tagliavini, Fabrizio, Santana, Isabel, Butler, Chris R, Ducharme, Simon, Gerhard, Alexander, Danek, Adrian, Levin, Johannes, Otto, Markus, Heller, Carolin, Sorbi, Sandro, Le Ber, Isabelle, Pasquier, Florence, Gobom, Johan, Brinkmalm, Ann, Blennow, Kaj, Zetterberg, Henrik, Rohrer, Jonathan D, Initiative, GENetic FTD, Nelson, Annabel, Bocchetta, Martina, Bouzigues, Arabella, Greaves, Caroline V, Cash, David, Thomas, David L, Todd, Emily, Benotmane, Hanya, Nicholas, Jennifer, Samra, Kiran, Shafei, Rachelle, Timberlake, Carolyn, Russell, Lucy L, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Peakman, Georgia, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Tiraboschi, Pietro, Prioni, Sara, Redaelli, Veronica, Convery, Rhian S, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, van Swieten, John C, Poos, Jackie, Papma, Janne M, Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Seelaar, Harro, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Neurology, Amsterdam Neuroscience - Neurodegeneration, Clinical Genetics, GENetic FTD Initiative, Poesen, Koen, Van Damme, Philip, Bruffaerts, rose, Vandenbulcke, Mathieu, Vogels, ann, Bocchetta, Martina [0000-0003-1814-5024], and Apollo - University of Cambridge Repository
Subjects: Synaptic dysfunction, Cognitive Neuroscience, cerebrospinal fluid [gamma-Synuclein], Medizin, cerebrospinal fluid [Syntaxin 1], Syntaxin 1, genetics [Mutation], tau Proteins, cerebrospinal fluid [Frontotemporal Dementia], frontotemporal dementia, beta-Synuclein, gamma-Synuclein, Settore BIO/13 - Biologia Applicata, Humans, ddc:610, genetics [C9orf72 Protein], genetics [Frontotemporal Dementia], Biology, genetics [beta-Synuclein], genetics [Syntaxin 1], C9orf72 Protein, synaptic dysfunction, cerebrospinal fluid [C9orf72 Protein], Research, Biomarkers, Frontotemporal dementia, Mutation, Neurogranin, Frontotemporal Dementia, biomarkers, genetics [Neurogranin], genetics [tau Proteins], Neurology, cerebrospinal fluid [Biomarkers], genetics [gamma-Synuclein], Neurology (clinical), Human medicine, cerebrospinal fluid [Neurogranin]
Abstract: Background Approximately a third of frontotemporal dementia (FTD) is genetic with mutations in three genes accounting for most of the inheritance: C9orf72, GRN, and MAPT. Impaired synaptic health is a common mechanism in all three genetic variants, so developing fluid biomarkers of this process could be useful as a readout of cellular dysfunction within therapeutic trials. Methods A total of 193 cerebrospinal fluid (CSF) samples from the GENetic FTD Initiative including 77 presymptomatic (31 C9orf72, 23 GRN, 23 MAPT) and 55 symptomatic (26 C9orf72, 17 GRN, 12 MAPT) mutation carriers as well as 61 mutation-negative controls were measured using a microflow LC PRM-MS set-up targeting 15 synaptic proteins: AP-2 complex subunit beta, complexin-2, beta-synuclein, gamma-synuclein, 14–3-3 proteins (eta, epsilon, zeta/delta), neurogranin, Rab GDP dissociation inhibitor alpha (Rab GDI alpha), syntaxin-1B, syntaxin-7, phosphatidylethanolamine-binding protein 1 (PEBP-1), neuronal pentraxin receptor (NPTXR), neuronal pentraxin 1 (NPTX1), and neuronal pentraxin 2 (NPTX2). Mutation carrier groups were compared to each other and to controls using a bootstrapped linear regression model, adjusting for age and sex. Results CSF levels of eight proteins were increased only in symptomatic MAPT mutation carriers (compared with controls) and not in symptomatic C9orf72 or GRN mutation carriers: beta-synuclein, gamma-synuclein, 14–3-3-eta, neurogranin, Rab GDI alpha, syntaxin-1B, syntaxin-7, and PEBP-1, with three other proteins increased in MAPT mutation carriers compared with the other genetic groups (AP-2 complex subunit beta, complexin-2, and 14–3-3 zeta/delta). In contrast, CSF NPTX1 and NPTX2 levels were affected in all three genetic groups (decreased compared with controls), with NPTXR concentrations being affected in C9orf72 and GRN mutation carriers only (decreased compared with controls). No changes were seen in the CSF levels of these proteins in presymptomatic mutation carriers. Concentrations of the neuronal pentraxins were correlated with brain volumes in the presymptomatic period for the C9orf72 and GRN groups, suggesting that they become abnormal in proximity to symptom onset. Conclusions Differential synaptic impairment is seen in the genetic forms of FTD, with abnormalities in multiple measures in those with MAPT mutations, but only changes in neuronal pentraxins within the GRN and C9orf72 mutation groups. Such markers may be useful in future trials as measures of synaptic dysfunction, but further work is needed to understand how these markers change throughout the course of the disease.
Published: 2022

47. Combining balneotherapy and health promotion to promote active and healthy ageing: the Balaruc-MACVIA-LR® approach

Author: Blain, H., Bernard, P. L., Canovas, G., Raffort, N., Desfour, H., Soriteau, L., Noguès, M., Camuzat, T., Mercier, J., Dupeyron, A., Quéré, I., Laffont, I., Hérisson, C., Solimene, H., and Bousquet, J.
Published: 2016
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48. A unique common ancestor introduced P301L mutation in MAPT gene in frontotemporal dementia patients from Barcelona (Baix Llobregat, Spain)

Author: Palencia-Madrid, Leire, Sánchez-Valle, Raquel, Fernández de Retana, Ierai, Borrego, Sergi, Grau-Rivera, Oriol, Reñé, Ramón, Hernández, Isabel, Almenar, Consuelo, Rossi, Giacomina, Caroppo, Paola, Redaelli, Veronica, Le Ber, Isabelle, Camuzat, Agnès, Brice, Alexis, Antonell, Anna, Balasa, Mircea, Gelpi, Ellen, Lladó, Albert, and de Pancorbo, Marian M.
Published: 2019
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49. New Antibody-Free Mass Spectrometry-Based Quantification Reveals That C9ORF72 Long Protein Isoform Is Reduced in the Frontal Cortex of Hexanucleotide-Repeat Expansion Carriers

Author: Arthur Viodé, Clémence Fournier, Agnès Camuzat, François Fenaille, NeuroCEB Brain Bank, Morwena Latouche, Fanny Elahi, Isabelle Le Ber, Christophe Junot, Foudil Lamari, Vincent Anquetil, François Becher, Franck Letournel, Anne Vital, Françoise Chapon, Catherine Godfraind, Claude-Alain Maurage, Vincent Deramecourt, David Meyronnet, Nathalie Streichenberger, André Maues de Paula, Valérie Rigau, Fanny Vandenbos-Burel, Charles Duyckaerts, Danielle Seilhean, Véronique Sazdovitch, Serge Milin, Dan Christian Chiforeanu, Annie Laquerrière, and Béatrice Lannes
Subjects: frontotemporal dementia (FTD), frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), C9ORF72, TDP-43, TDP43, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Frontotemporal dementia (FTD) is a fatal neurodegenerative disease characterized by behavioral and language disorders. The main genetic cause of FTD is an intronic hexanucleotide repeat expansion (G4C2)n in the C9ORF72 gene. A loss of function of the C9ORF72 protein associated with the allele-specific reduction of C9ORF72 expression is postulated to contribute to the disease pathogenesis. To better understand the contribution of the loss of function to the disease mechanism, we need to determine precisely the level of reduction in C9ORF72 long and short isoforms in brain tissue from patients with C9ORF72 mutations. In this study, we developed a sensitive and robust mass spectrometry (MS) method for quantifying C9ORF72 isoform levels in human brain tissue without requiring antibody or affinity reagent. An optimized workflow based on surfactant-aided protein extraction and pellet digestion was established for optimal recovery of the two isoforms in brain samples. Signature peptides, common or specific to the isoforms, were targeted in brain extracts by multiplex MS through the parallel reaction monitoring mode on a Quadrupole–Orbitrap high resolution mass spectrometer. The assay was successfully validated and subsequently applied to frontal cortex brain samples from a cohort of FTD patients with C9ORF72 mutations and neurologically normal controls without mutations. We showed that the C9ORF72 short isoform in the frontal cortices is below detection threshold in all tested individuals and the C9ORF72 long isoform is significantly decreased in C9ORF72 mutation carriers.
Published: 2018
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50. France A Chronicle of French Family Law: 2020

Author: Christine Bidaud, Hugues Fulchiron, Massilia Ajvizal, Bastien Baret, Claire Brunerie, Aurore Camuzat, Éric Fongaro, Guillaume Kessler, Guillaume Millerioux, Taylène Moreira De Sá, Mathilde Mosiek-Brasset, Margot Musson, and Richard Vessaud
Published: 2021

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