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121 results on '"Swift, Imogen J"'

1. A systematic review of progranulin concentrations in biofluids in over 7,000 people—assessing the pathogenicity of GRN mutations and other influencing factors

Author: Swift, Imogen J., Rademakers, Rosa, Finch, NiCole, Baker, Matt, Ghidoni, Roberta, Benussi, Luisa, Binetti, Giuliano, Rossi, Giacomina, Synofzik, Matthis, Wilke, Carlo, Mengel, David, Graff, Caroline, Takada, Leonel T., Sánchez-Valle, Raquel, Antonell, Anna, Galimberti, Daniela, Fenoglio, Chiara, Serpente, Maria, Arcaro, Marina, Schreiber, Stefanie, Vielhaber, Stefan, Arndt, Philipp, Santana, Isabel, Almeida, Maria Rosario, Moreno, Fermín, Barandiaran, Myriam, Gabilondo, Alazne, Stubert, Johannes, Gómez-Tortosa, Estrella, Agüero, Pablo, Sainz, M. José, Gohda, Tomohito, Murakoshi, Maki, Kamei, Nozomu, Kittel-Schneider, Sarah, Reif, Andreas, Weigl, Johannes, Jian, Jinlong, Liu, Chuanju, Serrero, Ginette, Greither, Thomas, Theil, Gerit, Lohmann, Ebba, Gazzina, Stefano, Bagnoli, Silvia, Coppola, Giovanni, Bruni, Amalia, Quante, Mirja, Kiess, Wieland, Hiemisch, Andreas, Jurkutat, Anne, Block, Matthew S., Carlson, Aaron M., Bråthen, Geir, Sando, Sigrid Botne, Grøntvedt, Gøril Rolfseng, Lauridsen, Camilla, Heslegrave, Amanda, Heller, Carolin, Abel, Emily, Gómez-Núñez, Alba, Puey, Roger, Arighi, Andrea, Rotondo, Enmanuela, Jiskoot, Lize C., Meeter, Lieke H. H., Durães, João, Lima, Marisa, Tábuas-Pereira, Miguel, Lemos, João, Boeve, Bradley, Petersen, Ronald C., Dickson, Dennis W., Graff-Radford, Neill R., LeBer, Isabelle, Sellami, Leila, Lamari, Foudil, Clot, Fabienne, Borroni, Barbara, Cantoni, Valentina, Rivolta, Jasmine, Lleó, Alberto, Fortea, Juan, Alcolea, Daniel, Illán-Gala, Ignacio, Andres-Cerezo, Lucie, Van Damme, Philip, Clarimon, Jordi, Steinacker, Petra, Feneberg, Emily, Otto, Markus, van der Ende, Emma L., van Swieten, John C., Seelaar, Harro, Zetterberg, Henrik, Sogorb-Esteve, Aitana, and Rohrer, Jonathan D.
Published: 2024
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2. Differential patterns of lysosomal dysfunction are seen in the clinicopathological forms of primary progressive aphasia

Author: Swift, Imogen J., Sjödin, Simon, Gobom, Johan, Brinkmalm, Ann, Blennow, Kaj, Zetterberg, Henrik, Rohrer, Jonathan D., and Sogorb-Esteve, Aitana
Published: 2024
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3. Network structure and transcriptomic vulnerability shape atrophy in frontotemporal dementia

Author: Shafiei, Golia, Bazinet, Vincent, Dadar, Mahsa, Manera, Ana L, Collins, D Louis, Dagher, Alain, Borroni, Barbara, Sanchez-Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Synofzik, Matthis, Galimberti, Daniela, Rowe, James B, Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, Vandenberghe, Rik, de Mendonça, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Butler, Chris, Gerhard, Alex, Danek, Adrian, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Jiskoot, Lize C, Seelaar, Harro, van Swieten, John C, Rohrer, Jonathan D, Misic, Bratislav, Ducharme, Simon, Initiative, Frontotemporal Lobar Degeneration Neuroimaging, Rosen, Howard, Dickerson, Bradford C, Domoto-Reilly, Kimoko, Knopman, David, Boeve, Bradley F, Boxer, Adam L, Kornak, John, Miller, Bruce L, Seeley, William W, Gorno-Tempini, Maria-Luisa, McGinnis, Scott, Mandelli, Maria Luisa, Initiative, GENetic Frontotemporal dementia, 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, van der Ende, Emma, Poos, Jackie, Papma, Janne M, Giannini, Lucia, and van Minkelen, Rick
Subjects: Biomedical and Clinical Sciences, Health Sciences, Psychology, Acquired Cognitive Impairment, Dementia, Aging, Neurodegenerative, Frontotemporal Dementia (FTD), Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Alzheimer's Disease, Aetiology, 2.1 Biological and endogenous factors, Neurological, Humans, Frontotemporal Dementia, Transcriptome, Brain, Pick Disease of the Brain, Atrophy, Connectome, Magnetic Resonance Imaging, Neuropsychological Tests, Frontotemporal Lobar Degeneration Neuroimaging Initiative, GENetic Frontotemporal dementia Initiative, connectome, disease epicentre, frontotemporal dementia, gene expression, network spreading, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences
Abstract: Connections among brain regions allow pathological perturbations to spread from a single source region to multiple regions. Patterns of neurodegeneration in multiple diseases, including behavioural variant of frontotemporal dementia (bvFTD), resemble the large-scale functional systems, but how bvFTD-related atrophy patterns relate to structural network organization remains unknown. Here we investigate whether neurodegeneration patterns in sporadic and genetic bvFTD are conditioned by connectome architecture. Regional atrophy patterns were estimated in both genetic bvFTD (75 patients, 247 controls) and sporadic bvFTD (70 patients, 123 controls). First, we identified distributed atrophy patterns in bvFTD, mainly targeting areas associated with the limbic intrinsic network and insular cytoarchitectonic class. Regional atrophy was significantly correlated with atrophy of structurally- and functionally-connected neighbours, demonstrating that network structure shapes atrophy patterns. The anterior insula was identified as the predominant group epicentre of brain atrophy using data-driven and simulation-based methods, with some secondary regions in frontal ventromedial and antero-medial temporal areas. We found that FTD-related genes, namely C9orf72 and TARDBP, confer local transcriptomic vulnerability to the disease, modulating the propagation of pathology through the connectome. Collectively, our results demonstrate that atrophy patterns in sporadic and genetic bvFTD are jointly shaped by global connectome architecture and local transcriptomic vulnerability, providing an explanation as to how heterogenous pathological entities can lead to the same clinical syndrome.
Published: 2023

4. Temporal order of clinical and biomarker changes in familial frontotemporal dementia

Author: Staffaroni, Adam M, Quintana, Melanie, Wendelberger, Barbara, Heuer, Hilary W, Russell, Lucy L, Cobigo, Yann, Wolf, Amy, Goh, Sheng-Yang Matt, Petrucelli, Leonard, Gendron, Tania F, Heller, Carolin, Clark, Annie L, Taylor, Jack Carson, Wise, Amy, Ong, Elise, Forsberg, Leah, Brushaber, Danielle, Rojas, Julio C, VandeVrede, Lawren, Ljubenkov, Peter, Kramer, Joel, Casaletto, Kaitlin B, Appleby, Brian, Bordelon, Yvette, Botha, Hugo, Dickerson, Bradford C, Domoto-Reilly, Kimiko, Fields, Julie A, Foroud, Tatiana, Gavrilova, Ralitza, 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, Jones, David T, Kantarci, Kejal, Kaufer, Daniel, Knopman, David, Kremers, Walter, Lago, Argentina Lario, Lapid, Maria I, Litvan, Irene, Lucente, Diane, Mackenzie, Ian R, Mendez, Mario F, Mester, Carly, Miller, Bruce L, Onyike, Chiadi U, Rademakers, Rosa, Ramanan, Vijay K, Ramos, Eliana Marisa, Rao, Meghana, Rascovsky, Katya, Rankin, Katherine P, Roberson, Erik D, Savica, Rodolfo, Tartaglia, M. Carmela, Weintraub, Sandra, Wong, Bonnie, Cash, David M, Bouzigues, Arabella, Swift, Imogen J, Peakman, Georgia, Bocchetta, Martina, 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, Jiskoot, Lize C, Sorbi, Sandro, Butler, Chris R, Graff, Caroline, Gerhard, Alexander, Langheinrich, Tobias, Laforce, Robert, Sanchez-Valle, Raquel, de MendonÃ§a, Alexandre, Moreno, Fermin, Synofzik, Matthis, Vandenberghe, Rik, Ducharme, Simon, Le Ber, Isabelle, Levin, Johannes, Danek, Adrian, Otto, Markus, Pasquier, Florence, Santana, Isabel, and Kornak, John
Published: 2022

5. Altered plasma protein profiles in genetic FTD – a GENFI study

Author: Ullgren, Abbe, Öijerstedt, Linn, Olofsson, Jennie, Bergström, Sofia, Remnestål, Julia, van Swieten, John C., Jiskoot, Lize C., Seelaar, Harro, Borroni, Barbara, Sanchez-Valle, Raquel, Moreno, Fermin, Laforce, Robert, Synofzik, Matthis, Galimberti, Daniela, Rowe, James B., Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, Vandenberghe, Rik, de Mendonça, Alexandre, Tirabosch, Pietro, Santana, Isabel, Ducharme, Simon, Butler, Chris R., Gerhard, Alexander, Otto, Markus, Bouzigues, Arabella, Russell, Lucy, Swift, Imogen J., Sogorb-Esteve, Aitana, Heller, Carolin, Rohrer, Jonathan D., Månberg, Anna, Nilsson, Peter, and Graff, Caroline
Published: 2023
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6. 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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7. Proteomic analysis reveals distinct cerebrospinal fluid signatures across genetic frontotemporal dementia subtypes.

Author: Sogorb-Esteve, Aitana, Weiner, Sophia, Simrén, Joel, Swift, Imogen J., Bocchetta, Martina, Todd, Emily G., Cash, David M., Bouzigues, Arabella, Russell, Lucy L., Foster, Phoebe H., Ferry-Bolder, Eve, van Swieten, John C., Jiskoot, Lize C., Seelaar, Harro, Sanchez-Valle, Raquel, Laforce, Robert, Graff, Caroline, Galimberti, Daniela, Vandenberghe, Rik, and de Mendonça, Alexandre
Subjects: FRONTOTEMPORAL dementia, ALZHEIMER'S patients, CARRIER proteins, CEREBROSPINAL fluid, GENE regulatory networks
Abstract: We used an untargeted mass spectrometric approach, tandem mass tag proteomics, for the identification of proteomic signatures in genetic frontotemporal dementia (FTD). A total of 238 cerebrospinal fluid (CSF) samples from the Genetic FTD Initiative were analyzed, including samples from 107 presymptomatic (44 C9orf72, 38 GRN, and 25 MAPT) and 55 symptomatic (27 C9orf72, 17 GRN, and 11 MAPT) mutation carriers as well as 76 mutation-negative controls ("noncarriers"). We found shared and distinct proteomic alterations in each genetic form of FTD. Among the proteins significantly altered in symptomatic mutation carriers compared with noncarriers, we found that a set of proteins including neuronal pentraxin 2 and fatty acid binding protein 3 changed across all three genetic forms of FTD and patients with Alzheimer's disease from previously published datasets. We observed differential changes in lysosomal proteins among symptomatic mutation carriers with marked abundance decreases in MAPT carriers but not other carriers. Further, we identified mutation-associated proteomic changes already evident in presymptomatic mutation carriers. Weighted gene coexpression network analysis combined with gene ontology annotation revealed clusters of proteins enriched in neurodegeneration and glial responses as well as synapse- or lysosome-related proteins indicating that these are the central biological processes affected in genetic FTD. These clusters correlated with measures of disease severity and were associated with cognitive decline. This study revealed distinct proteomic changes in the CSF of patients with genetic FTD, providing insights into the pathological processes involved in the disease. In addition, we identified proteins that warrant further exploration as diagnostic and prognostic biomarker candidates. Editor's summary: Familial frontotemporal dementia (FTD) is caused by mutations in risk genes, most commonly C9orf72, MAPT, or GRN. Here, Sogorb-Esteve et al. used untargeted mass spectrometry of cerebrospinal fluid samples from presymptomatic and symptomatic carriers of these three risk genes to characterize distinct and shared proteomic alterations. Weighted gene coexpression network analysis allowed grouping FTD-dysregulated proteins into modules with high coexpression patterns, highlighting potentially dysregulated biological pathways, such as "core markers," "synapse," and "actin binding." The expression of a subset of these modules was correlated with clinical scores. These results provide a useful resource for FTD research and disease marker development. —Daniela Neuhofer [ABSTRACT FROM AUTHOR]
Published: 2025
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8. Elevated CSF and plasma complement proteins in genetic frontotemporal dementia: results from the GENFI study

Author: van der Ende, Emma L., Heller, Carolin, Sogorb-Esteve, Aitana, Swift, Imogen J., McFall, David, Peakman, Georgia, Bouzigues, Arabella, Poos, Jackie M., Jiskoot, Lize C., Panman, Jessica L., Papma, Janne M., Meeter, Lieke H., Dopper, Elise G. P., Bocchetta, Martina, Todd, Emily, Cash, David, Graff, Caroline, Synofzik, Matthis, Moreno, Fermin, Finger, Elizabeth, Sanchez-Valle, Raquel, Vandenberghe, Rik, Laforce, Jr, Robert, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B., Butler, Chris, Ducharme, Simon, Gerhard, Alexander, Danek, Adrian, Levin, Johannes, Pijnenburg, Yolande A. L., Otto, Markus, Borroni, Barbara, Tagliavini, Fabrizio, de Mendonça, Alexandre, Santana, Isabel, Galimberti, Daniela, Sorbi, Sandro, Zetterberg, Henrik, Huang, Eric, van Swieten, John C., Rohrer, Jonathan D., and Seelaar, Harro
Published: 2022
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9. Differential impairment of cerebrospinal fluid synaptic biomarkers in the genetic forms of frontotemporal dementia

Author: Sogorb-Esteve, Aitana, Nilsson, Johanna, Swift, Imogen J., Heller, Carolin, Bocchetta, Martina, Russell, Lucy L., Peakman, Georgia, Convery, Rhian S., van Swieten, John C., Seelaar, Harro, Borroni, Barbara, Galimberti, Daniela, Sanchez-Valle, Raquel, Laforce, Jr., Robert, Moreno, Fermin, Synofzik, Matthis, Graff, Caroline, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B., Vandenberghe, Rik, Finger, Elizabeth, Tagliavini, Fabrizio, Santana, Isabel, Butler, Chris R., Ducharme, Simon, Gerhard, Alexander, Danek, Adrian, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Le Ber, Isabelle, Pasquier, Florence, Gobom, Johan, Brinkmalm, Ann, Blennow, Kaj, Zetterberg, Henrik, and Rohrer, Jonathan D.
Published: 2022
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10. Differential chemokine alteration in the variants of primary progressive aphasia—a role for neuroinflammation

Author: Sogorb-Esteve, Aitana, Swift, Imogen J., Woollacott, Ione O. C., Warren, Jason D., Zetterberg, Henrik, and Rohrer, Jonathan D.
Published: 2021
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11. Development of a targeted proteomic assay for the quantitation of neurofilament light in cerebrospinal fluid: Correlation with Simoa‐based quantitation across neurodegenerative diseases and centres

Author: Leckey, Claire A., primary, Coulton, John, additional, Barthélemy, Nicolas R., additional, He, Yingxin, additional, Laban, Rhiannon, additional, Heslegrave, Amanda, additional, Giovannucci, Tatiana A., additional, Byrne, Lauren M, additional, Swift, Imogen J, additional, Esteve, Aitana Sogorb, additional, Rohrer, Jonathan D., additional, Schott, Jonathan M, additional, Wild, Edward J, additional, Zetterberg, Henrik, additional, Wray, Selina, additional, Mills, Kevin, additional, Bateman, Randall J., additional, and Paterson, Ross W., additional
Published: 2023
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12. Targeted proteomic search reveals new actors in the synaptic and lysosomal dysfunction in genetic FTD, a GENFI study.

Author: Weiner, Sophia, primary, Malichova, Frederika, additional, Simrén, Joel, additional, Sauer, Mathias, additional, Swift, Imogen J, additional, Heller, Carolin, additional, Knowles, Kathryn, additional, van Swieten, John C., additional, Jiskoot, Lize C., additional, Seelaar, Harro, additional, Moreno, Fermin, additional, Sanchez‐Valle, Raquel, additional, Laforce, Robert, additional, Graff, Caroline, additional, Masellis, Mario, additional, Tartaglia, 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, Christopher, additional, Gerhard, Alexander, additional, Ducharme, Simon, additional, Ber, Isabelle Le, additional, Tiraboschi, Pietro, additional, Santana, Isabel, additional, Pasquier, Florence, additional, Levin, Johannes, additional, Otto, Markus, additional, Sorbi, Sandro, additional, Blennow, Kaj, additional, Zetterberg, Henrik, additional, Rohrer, Jonathan D., additional, Gobom, Johan, additional, and Esteve, Aitana Sogorb, additional
Published: 2023
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13. Optimising remote sampling of NfL and GFAP using blood cards in the Genetic Frontotemporal Dementia Initiative (GENFI) cohort

Author: Goldsmith, Sophie E, primary, Swift, Imogen J, additional, Oh, Lara, additional, Laban, Rhiannon, additional, Zetterberg, Henrik, additional, Esteve, Aitana Sogorb, additional, and Rohrer, Jonathan D., additional
Published: 2023
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14. Developing a mass spectrometric assay to measure granulin peptides in CSF for progranulin‐associated frontotemporal dementia

Author: Swift, Imogen J, primary, Weiner, Sophia, additional, Sauer, Mathias, additional, Nilsson, Johanna, additional, van Swieten, John C., additional, Jiskoot, Lize C., additional, Seelaar, Harro, additional, Moreno, Fermin, additional, Sánchez‐Valle, Raquel, additional, Laforce, Robert, additional, Graff, Caroline, additional, Masellis, Mario, additional, Tartaglia, 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, Christopher, additional, Gerhard, Alexander, additional, Ducharme, Simon, additional, Ber, Isabelle Le, additional, Tiraboschi, Pietro, additional, Santana, Isabel, additional, Pasquier, Florence, additional, Levin, Johannes, additional, Otto, Markus, additional, Sorbi, Sandro, additional, Brinkmalm, Ann, additional, Zetterberg, Henrik, additional, Rohrer, Jonathan D., additional, Esteve, Aitana Sogorb, additional, and Gobom, Johan, additional
Published: 2023
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15. 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
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16. Characterizing the Clinical Features and Atrophy Patterns of MAPT-Related Frontotemporal Dementia With Disease Progression Modeling

Author: Young, Alexandra L., Bocchetta, Martina, Russell, Lucy L., Convery, Rhian S., Peakman, Georgia, Todd, Emily, Cash, David M., Greaves, Caroline V., van Swieten, John, Jiskoot, Lize, Seelaar, Harro, Moreno, Fermin, Sanchez-Valle, Raquel, Borroni, Barbara, Laforce, Robert, Jr, Masellis, Mario, Tartaglia, Maria Carmela, Graff, Caroline, Galimberti, Daniela, Rowe, James B., Finger, Elizabeth, Synofzik, Matthis, Vandenberghe, Rik, de Mendonça, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Ducharme, Simon, Butler, Chris, Gerhard, Alex, Levin, Johannes, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Williams, Steven C.R., Alexander, Daniel C., Rohrer, Jonathan D., Rossor, Martin N., Fox, Nick C., Warren, Jason D., Woollacott, Ione, Shafei, Rachelle, Heller, Carolin, Swift, Imogen J, Moore, Katrina, Guerreiro, Rita, Bras, Jose, Thomas, David L., Nicholas, Jennifer, Mead, Simon, Meeter, Lieke, Panman, Jessica, Papma, Janne M., Poos, Jackie, van Minkelen, Rick, Pijnenburg, Yolande, Barandiaran, Myriam, Indakoetxea, Begoña, Gabilondo, Alazne, Tainta, Mikel, de Arriba, María, Gorostidi, Ana, Zulaica, Miren, Villanua, Jorge, Díaz, Zigor, Borrego-Ecija, Sergi, Olives, Jaume, Lladó, Albert, Balasa, Mircea, Antonell, Anna, Bargalló, Nuria, Premi, Enrico, Cosseddu, Maura, Gazzina, Stefano, Padovani, Alessandro, Gasparotti, Roberto, Archetti, Silvana, Black, Sandra, Mitchell, Sara, Rogaeva, Ekaterina, Freedman, Morris, Keren, Ron, Tang-Wai, David, Öijerstedt, Linn, Andersson, Christin, Jelic, Vesna, Thonberg, Hakan, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Cope, Thomas, Timberlake, Carolyn, Rittman, Timothy, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Wilke, Carlo, Karnath, Hans Otto, Bender, Benjamin, Bruffaerts, Rose, Van Damme, Philip, Vandenbulcke, Mathieu, Ferreira, Catarina B., Miltenberger, Gabriel, Maruta, Carolina, Verdelho, Ana, Afonso, Sónia, Taipa, Ricardo, Caroppo, Paola, Di Fede, Giuseppe, Giaccone, Giorgio, Prioni, Sara, Redaelli, Veronica, Rossi, Giacomina, Tiraboschi, Pietro, Duro, Diana, Almeida, Maria Rosario, Branco, Miguel Castelo, Leitão, Maria João, Pereira, Miguel Tábuas, Santiago, Beatriz, Gauthier, Serge, Neto, Pedro Rosa, Veldsman, Michele, Thompson, Paul, Prix, Catharina, Hoegen, Tobias, Mag.rer.nat, Elisabeth Wlasich, Loosli, Sandra, Schönecker, Sonja, Dr.hum.bio, Elisa Semler, Psych, Dipl., Anderl-Straub, Sarah, Psych, Dipl., Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, and Bessi, Valentina
Published: 2021
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17. Variable clinical phenotype in TBK1 mutations: case report of a novel mutation causing primary progressive aphasia and review of the literature

Author: Swift, Imogen J., Bocchetta, Martina, Benotmane, Hanya, Woollacott, Ione OC., Shafei, Rachelle, and Rohrer, Jonathan D.
Published: 2021
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18. 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
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19. 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
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20. 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
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21. Early neurotransmitters changes in prodromal frontotemporal dementia: A GENFI study

Author: Premi, Enrico, primary, Pengo, Marta, additional, Mattioli, Irene, additional, Cantoni, Valentina, additional, Dukart, Juergen, additional, Gasparotti, Roberto, additional, Buratti, Emanuele, additional, Padovani, Alessandro, additional, Bocchetta, Martina, additional, Todd, Emily G., additional, Bouzigues, Arabella, additional, Cash, David M., additional, Convery, Rhian S., additional, Russell, Lucy L., additional, Foster, Phoebe, additional, Thomas, David L., additional, van Swieten, John C., additional, Jiskoot, Lize C., additional, Seelaar, Harro, additional, Galimberti, Daniela, additional, Sanchez-Valle, Raquel, additional, Laforce, Robert, additional, Moreno, Fermin, additional, Synofzik, Matthis, additional, Graff, Caroline, additional, Masellis, Mario, additional, Tartaglia, Maria Carmela, additional, Rowe, James B., additional, Tsvetanov, Kamen A., additional, Vandenberghe, Rik, additional, Finger, Elizabeth, additional, Tiraboschi, Pietro, additional, de Mendonça, Alexandre, additional, Santana, Isabel, additional, Butler, Chris R., additional, Ducharme, Simon, additional, Gerhard, Alexander, additional, Levin, Johannes, additional, Otto, Markus, additional, Sorbi, Sandro, additional, Le Ber, Isabelle, additional, Pasquier, Florence, additional, Rohrer, Jonathan D., additional, Borroni, Barbara, additional, Esteve, Aitana Sogorb, additional, Heller, Carolin, additional, Greaves, Caroline V., additional, Zetterberg, Henrik, additional, Swift, Imogen J., additional, Samra, Kiran, additional, Shafei, Rachelle, additional, Timberlake, Carolyn, additional, Cope, Thomas, additional, Rittman, Timothy, 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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22. Seed amplification and neurodegeneration marker trajectories in individuals at risk of prion disease

Author: Mok, Tze How, primary, Nihat, Akin, additional, Majbour, Nour, additional, Sequeira, Danielle, additional, Holm-Mercer, Leah, additional, Coysh, Thomas, additional, Darwent, Lee, additional, Batchelor, Mark, additional, Groveman, Bradley R, additional, Orr, Christina D, additional, Hughson, Andrew G, additional, Heslegrave, Amanda, additional, Laban, Rhiannon, additional, Veleva, Elena, additional, Paterson, Ross W, additional, Keshavan, Ashvini, additional, Schott, Jonathan M, additional, Swift, Imogen J, additional, Heller, Carolin, additional, Rohrer, Jonathan D, additional, Gerhard, Alexander, additional, Butler, Christopher, additional, Rowe, James B, additional, Masellis, Mario, additional, Chapman, Miles, additional, Lunn, Michael P, additional, Bieschke, Jan, additional, Jackson, Graham S, additional, Zetterberg, Henrik, additional, Caughey, Byron, additional, Rudge, Peter, additional, Collinge, John, additional, and Mead, Simon, additional
Published: 2023
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23. 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
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24. 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
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25. Neurofilament light oligomers in neurodegenerative diseases: quantification by homogeneous immunoassay in cerebrospinal fluid

Author: Meda, Francisco J., primary, Knowles, Kathryn, additional, Swift, Imogen J., additional, Sogorb-Esteve, Aitana, additional, Rohrer, Jonathan D., additional, Dittrich, Anna, additional, Skoog, Ingmar, additional, Kern, Silke, additional, Becker, Bruno, additional, Blennow, Kaj, additional, Andreasson, Ulf, additional, Kvartsberg, Hlin, additional, and Zetterberg, Henrik, additional
Published: 2023
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26. C5F glial markers are elevated in a subset of patients with genetic frontotemporal dementia

Author: Woollacott, Ione OC, Swift, Imogen J, Sogorb-Esteve, Aitana, Heller, Carolin, Knowles, Kathryn, Bouzigues, Arabella, Russell, Lucy L, Peakman, Georgia, Greaves, Caroline, Convery, Rhian, Heslegrave, Amanda, Rowe, James B, Borroni, Barbara, Galimberti, Daniela, Tiraboschi, Pietro, Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, van Swieten, John C, Seelaar, Harro, Jiskoot, Lize, Sorbi, Sandro, Butler, Chris R, Graff, Caroline, Gerhard, Alexander, Laforce, Robert, Sanchez-Valle, Raquel, de Mendonca, Alexandre, Moreno, Fermin, Synofzik, Matthis, Vandenberghe, Rik, Ducharme, Simon, Le Ber, Isabelle, Levin, Johannes, Otto, Markus, Pasquier, Florence, Santana, Isabel, Zetterberg, Henrik, and Rohrer, Jonathan D
Subjects: MICROGLIA, Science & Technology, FLUID BIOMARKERS, Clinical Neurology, Neurosciences, INJURY, Neurosciences & Neurology, LOBAR DEGENERATION, Life Sciences & Biomedicine, GENFI
Abstract: BACKGROUND: Neuroinflammation has been shown to be an important pathophysiological disease mechanism in frontotemporal dementia (FTD). This includes activation of microglia, a process that can be measured in life through assaying different glia-derived biomarkers in cerebrospinal fluid. However, only a few studies so far have taken place in FTD, and even fewer focusing on the genetic forms of FTD. METHODS: We investigated the cerebrospinal fluid concentrations of TREM2, YKL-40 and chitotriosidase using immunoassays in 183 participants from the Genetic FTD Initiative (GENFI) study: 49 C9orf72 (36 presymptomatic, 13 symptomatic), 49 GRN (37 presymptomatic, 12 symptomatic) and 23 MAPT (16 presymptomatic, 7 symptomatic) mutation carriers and 62 mutation-negative controls. Concentrations were compared between groups using a linear regression model adjusting for age and sex, with 95% bias-corrected bootstrapped confidence intervals. Concentrations in each group were correlated with the Mini-Mental State Examination (MMSE) score using non-parametric partial correlations adjusting for age. Age-adjusted z-scores were also created for the concentration of markers in each participant, investigating how many had a value above the 95th percentile of controls. RESULTS: Only chitotriosidase in symptomatic GRN mutation carriers had a concentration significantly higher than controls. No group had higher TREM2 or YKL-40 concentrations than controls after adjusting for age and sex. There was a significant negative correlation of chitotriosidase concentration with MMSE in presymptomatic GRN mutation carriers. In the symptomatic groups, for TREM2 31% of C9orf72, 25% of GRN, and 14% of MAPT mutation carriers had a concentration above the 95th percentile of controls. For YKL-40 this was 8% C9orf72, 8% GRN and 0% MAPT mutation carriers, whilst for chitotriosidase it was 23% C9orf72, 50% GRN, and 29% MAPT mutation carriers. CONCLUSIONS: Although chitotriosidase concentrations in GRN mutation carriers were the only significantly raised glia-derived biomarker as a group, a subset of mutation carriers in all three groups, particularly for chitotriosidase and TREM2, had elevated concentrations. Further work is required to understand the variability in concentrations and the extent of neuroinflammation across the genetic forms of FTD. However, the current findings suggest limited utility of these measures in forthcoming trials. ispartof: ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY vol:9 issue:11 pages:1764-1777 ispartof: location:United States status: published
Published: 2022

27. CSF glial markers are elevated in a subset of patients with genetic frontotemporal dementia

Author: the Genetic FTD Initiative, GENFI, Woollacott, Ione O.C., Swift, Imogen J., Sogorb-Esteve, Aitana, Heller, Carolin, Knowles, Kathryn, Bouzigues, Arabella, Russell, Lucy L., Peakman, Georgia, Greaves, Caroline V., Convery, Rhian, Heslegrave, Amanda, Rowe, James B., Borroni, Barbara, Galimberti, Daniela, Tiraboschi, Pietro, Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, van Swieten, John C., Seelaar, Harro, Jiskoot, Lize, Sorbi, Sandro, Butler, Chris R., Graff, Caroline, Gerhard, Alexander, Laforce, Robert, Sanchez-Valle, Raquel, de Mendonça, Alexandre, Moreno, Fermin, Synofzik, Matthis, Vandenberghe, Rik, Ducharme, Simon, Ber, Isabelle Le, Levin, Johannes, Otto, Markus, Pasquier, Florence, Santana, Isabel, Zetterberg, Henrik, Rohrer, Jonathan D., Nelson, Annabel, Bocchetta, Martina, Cash, David, Thomas, David L., Todd, Emily, Benotmane, Hanya, Nicholas, Jennifer, Samra, Kiran, Maruta, Carolina, do Couto, Frederico Simões, Almeida, Maria Rosário, and Veritati - Repositório Institucional da Universidade Católica Portuguesa
Abstract: Background: Neuroinflammation has been shown to be an important pathophysiological disease mechanism in frontotemporal dementia (FTD). This includes activation of microglia, a process that can be measured in life through assaying different glia-derived biomarkers in cerebrospinal fluid. However, only a few studies so far have taken place in FTD, and even fewer focusing on the genetic forms of FTD. Methods: We investigated the cerebrospinal fluid concentrations of TREM2, YKL-40 and chitotriosidase using immunoassays in 183 participants from the Genetic FTD Initiative (GENFI) study: 49 C9orf72 (36 presymptomatic, 13 symptomatic), 49 GRN (37 presymptomatic, 12 symptomatic) and 23 MAPT (16 presymptomatic, 7 symptomatic) mutation carriers and 62 mutation-negative controls. Concentrations were compared between groups using a linear regression model adjusting for age and sex, with 95% bias-corrected bootstrapped confidence intervals. Concentrations in each group were correlated with the Mini-Mental State Examination (MMSE) score using non-parametric partial correlations adjusting for age. Age-adjusted z-scores were also created for the concentration of markers in each participant, investigating how many had a value above the 95th percentile of controls. Results: Only chitotriosidase in symptomatic GRN mutation carriers had a concentration significantly higher than controls. No group had higher TREM2 or YKL-40 concentrations than controls after adjusting for age and sex. There was a significant negative correlation of chitotriosidase concentration with MMSE in presymptomatic GRN mutation carriers. In the symptomatic groups, for TREM2 31% of C9orf72, 25% of GRN, and 14% of MAPT mutation carriers had a concentration above the 95th percentile of controls. For YKL-40 this was 8% C9orf72, 8% GRN and 0% MAPT mutation carriers, whilst for chitotriosidase it was 23% C9orf72, 50% GRN, and 29% MAPT mutation carriers. Conclusions: Although chitotriosidase concentrations in GRN mutation carriers were the only significantly raised glia-derived biomarker as a group, a subset of mutation carriers in all three groups, particularly for chitotriosidase and TREM2, had elevated concentrations. Further work is required to understand the variability in concentrations and the extent of neuroinflammation across the genetic forms of FTD. However, the current findings suggest limited utility of these measures in forthcoming trials.
Published: 2022

28. Trajectories of neurodegeneration and seed amplification biomarkers prior to disease onset in individuals at risk of prion disease

Author: Mok, Tze How, primary, Nihat, Akin, additional, Majbour, Nour, additional, Sequeira, Danielle, additional, Holm-Mercer, Leah, additional, Coysh, Thomas, additional, Darwent, Lee, additional, Batchelor, Mark, additional, Groveman, Bradley R, additional, Orrù, Christina D, additional, Hughson, Andrew G, additional, Heslegrave, Amanda, additional, Laban, Rhiannon, additional, Veleva, Elena, additional, Paterson, Ross W, additional, Keshavan, Ashvini, additional, Schott, Jonathan, additional, Swift, Imogen J, additional, Heller, Carolin, additional, Rohrer, Jonathan D, additional, Gerhard, Alexander, additional, Butler, Christopher, additional, Rowe, James B, additional, Masellis, Mario, additional, Chapman, Miles, additional, Lunn, Michael P, additional, Bieschke, Jan, additional, Jackson, Graham, additional, Zetterberg, Henrik, additional, Caughey, Byron, additional, Rudge, Peter, additional, Collinge, John, additional, and Mead, Simon, additional
Published: 2022
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29. Development of a sensitive trial-ready poly(GP) CSF biomarker assay for C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis

Author: Wilson, Katherine M, Katona, Eszter, Glaria, Idoia, Carcolé, Mireia, Swift, Imogen J, Sogorb-Esteve, Aitana, Heller, Carolin, Bouzigues, Arabella, Heslegrave, Amanda J, Keshavan, Ashvini, Knowles, Kathryn, Patil, Saurabh, Mohapatra, Susovan, Liu, Yuanjing, Goyal, Jaya, Sanchez-Valle, Raquel, Laforce, Robert, Synofzik, Matthis, Rowe, James B, Finger, Elizabeth, Vandenberghe, Rik, Butler, Christopher R, Gerhard, Alexander, Van Swieten, John C, Seelaar, Harro, Borroni, Barbara, Galimberti, Daniela, De Mendonça, Alexandre, Masellis, Mario, Tartaglia, M Carmela, Otto, Markus, Graff, Caroline, Ducharme, Simon, Schott, Jonathan M, Malaspina, Andrea, Zetterberg, Henrik, Boyanapalli, Ramakrishna, Rohrer, Jonathan D, Isaacs, Adrian M, Genetic FTD Initiative (GENFI), Carcolé, Mireia [0000-0001-5054-9016], Heller, Carolin [0000-0002-1934-6162], Synofzik, Matthis [0000-0002-2280-7273], Rowe, James B [0000-0001-7216-8679], Finger, Elizabeth [0000-0003-4461-7427], Gerhard, Alexander [0000-0002-8071-6062], Van Swieten, John C [0000-0001-6278-6844], Seelaar, Harro [0000-0003-1989-7527], Borroni, Barbara [0000-0001-9340-9814], Galimberti, Daniela [0000-0002-9284-5953], Ducharme, Simon [0000-0002-7309-1113], Schott, Jonathan M [0000-0003-2059-024X], Zetterberg, Henrik [0000-0003-3930-4354], Rohrer, Jonathan D [0000-0002-6155-8417], Isaacs, Adrian M [0000-0002-6820-5534], and Apollo - University of Cambridge Repository
Subjects: MOTOR NEURON DISEASE, DNA Repeat Expansion, C9orf72 Protein, Frontotemporal Dementia, Amyotrophic Lateral Sclerosis, Humans, Biomarkers
Abstract: Funder: Bluefield Project, Funder: Fidelity Foundation; FundRef: http://dx.doi.org/10.13039/100005639, Funder: European Reference Network for Rare Neurological Diseases, Funder: Wellcome Trust; FundRef: http://dx.doi.org/10.13039/100010269, Funder: EU Joint Programme - Neurodegenerative Disease Research, OBJECTIVE: A GGGGCC repeat expansion in the C9orf72 gene is the most common cause of genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). As potential therapies targeting the repeat expansion are now entering clinical trials, sensitive biomarker assays of target engagement are urgently required. Our objective was to develop such an assay. METHODS: We used the single molecule array (Simoa) platform to develop an immunoassay for measuring poly(GP) dipeptide repeat proteins (DPRs) generated by the C9orf72 repeat expansion in cerebrospinal fluid (CSF) of people with C9orf72-associated FTD/ALS. RESULTS AND CONCLUSIONS: We show the assay to be highly sensitive and robust, passing extensive qualification criteria including low intraplate and interplate variability, a high precision and accuracy in measuring both calibrators and samples, dilutional parallelism, tolerance to sample and standard freeze-thaw and no haemoglobin interference. We used this assay to measure poly(GP) in CSF samples collected through the Genetic FTD Initiative (N=40 C9orf72 and 15 controls). We found it had 100% specificity and 100% sensitivity and a large window for detecting target engagement, as the C9orf72 CSF sample with the lowest poly(GP) signal had eightfold higher signal than controls and on average values from C9orf72 samples were 38-fold higher than controls, which all fell below the lower limit of quantification of the assay. These data indicate that a Simoa-based poly(GP) DPR assay is suitable for use in clinical trials to determine target engagement of therapeutics aimed at reducing C9orf72 repeat-containing transcripts.
Published: 2022

30. A data-driven disease progression model of fluid biomarkers in genetic frontotemporal dementia

Author: van der Ende, Emma L., Bron, Esther E., Poos, Jackie M., Jiskoot, Lize C., Panman, Jessica L., Papma, Janne M., Meeter, Lieke H., Dopper, Elise G.P., Wilke, Carlo, Synofzik, Matthis, Heller, Carolin, Swift, Imogen J., Sogorb-Esteve, Aitana, Bouzigues, Arabella, Borroni, Barbara, Sanchez-Valle, Raquel, Moreno, Fermin, Graff, Caroline, Laforce, Robert, Galimberti, Daniela, Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, Vandenberghe, Rik, Rowe, James B., de Mendonça, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Ducharme, Simon, Butler, Christopher R., Gerhard, Alexander, Levin, Johannes, Danek, Adrian, Otto, Markus, Pijnenburg, Yolande A.L., Sorbi, Sandro, Zetterberg, Henrik, Niessen, Wiro J., Rohrer, Jonathan D., Klein, Stefan, van Swieten, John C., Venkatraghavan, Vikram, Seelaar, Harro, van der Ende, Emma L., Bron, Esther E., Poos, Jackie M., Jiskoot, Lize C., Panman, Jessica L., Papma, Janne M., Meeter, Lieke H., Dopper, Elise G.P., Wilke, Carlo, Synofzik, Matthis, Heller, Carolin, Swift, Imogen J., Sogorb-Esteve, Aitana, Bouzigues, Arabella, Borroni, Barbara, Sanchez-Valle, Raquel, Moreno, Fermin, Graff, Caroline, Laforce, Robert, Galimberti, Daniela, Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, Vandenberghe, Rik, Rowe, James B., de Mendonça, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Ducharme, Simon, Butler, Christopher R., Gerhard, Alexander, Levin, Johannes, Danek, Adrian, Otto, Markus, Pijnenburg, Yolande A.L., Sorbi, Sandro, Zetterberg, Henrik, Niessen, Wiro J., Rohrer, Jonathan D., Klein, Stefan, van Swieten, John C., Venkatraghavan, Vikram, and Seelaar, Harro
Abstract: Several CSF and blood biomarkers for genetic frontotemporal dementia have been proposed, including those reflecting neuroaxonal loss (neurofilament light chain and phosphorylated neurofilament heavy chain), synapse dysfunction [neuronal pentraxin 2 (NPTX2)], astrogliosis (glial fibrillary acidic protein) and complement activation (C1q, C3b). Determining the sequence in which biomarkers become abnormal over the course of disease could facilitate disease staging and help identify mutation carriers with prodromal or early-stage frontotemporal dementia, which is especially important as pharmaceutical trials emerge. We aimed to model the sequence of biomarker abnormalities in presymptomatic and symptomatic genetic frontotemporal dementia using cross-sectional data from the Genetic Frontotemporal dementia Initiative (GENFI), a longitudinal cohort study. Two-hundred and seventy-five presymptomatic and 127 symptomatic carriers of mutations in GRN, C9orf72 or MAPT, as well as 247 non-carriers, were selected from the GENFI cohort based on availability of one or more of the aforementioned biomarkers. Nine presymptomatic carriers developed symptoms within 18 months of sample collection ('converters'). Sequences of biomarker abnormalities were modelled for the entire group using discriminative event-based modelling (DEBM) and for each genetic subgroup using co-initialized DEBM. These models estimate probabilistic biomarker abnormalities in a data-driven way and do not rely on previous diagnostic information or biomarker cut-off points. Using cross-validation, subjects were subsequently assigned a disease stage based on their position along the disease progression timeline. CSF NPTX2 was the first biomarker to become abnormal, followed by blood and CSF neurofilament light chain, blood phosphorylated neurofilament heavy chain, blood glial fibrillary acidic protein and finally CSF C3b and C1q. Biomarker orderings did not differ significantly between genetic subgroups, but more u
Published: 2022

31. Development of a sensitive trial-ready poly(GP) CSF biomarker assay for C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis

Author: Wilson, Katherine M., Katona, Eszter, Glaria, Idoia, Carcolé, Mireia, Swift, Imogen J., Sogorb-Esteve, Aitana, Heller, Carolin, Bouzigues, Arabella, Heslegrave, Amanda J., Keshavan, Ashvini, Knowles, Kathryn, Patil, Saurabh, Mohapatra, Susovan, Liu, Yuanjing, Goyal, Jaya, Sanchez-Valle, Raquel, Laforce, Robert Jr, Synofzik, Matthis, Rowe, James B., Finger, Elizabeth, Vandenberghe, Rik, Butler, Christopher R., Gerhard, Alexander, Van Swieten, John C., Seelaar, Harro, Borroni, Barbara, Galimberti, Daniela, De Mendonça, Alexandre, Masellis, Mario, Tartaglia, M. Carmela, Otto, Markus, Graff, Caroline, Ducharme, Simon, Schott, Jonathan M., Malaspina, Andrea, Zetterberg, Henrik, Boyanapalli, Ramakrishna, Rohrer, Jonathan D., Isaacs, Adrian M., Wilson, Katherine M., Katona, Eszter, Glaria, Idoia, Carcolé, Mireia, Swift, Imogen J., Sogorb-Esteve, Aitana, Heller, Carolin, Bouzigues, Arabella, Heslegrave, Amanda J., Keshavan, Ashvini, Knowles, Kathryn, Patil, Saurabh, Mohapatra, Susovan, Liu, Yuanjing, Goyal, Jaya, Sanchez-Valle, Raquel, Laforce, Robert Jr, Synofzik, Matthis, Rowe, James B., Finger, Elizabeth, Vandenberghe, Rik, Butler, Christopher R., Gerhard, Alexander, Van Swieten, John C., Seelaar, Harro, Borroni, Barbara, Galimberti, Daniela, De Mendonça, Alexandre, Masellis, Mario, Tartaglia, M. Carmela, Otto, Markus, Graff, Caroline, Ducharme, Simon, Schott, Jonathan M., Malaspina, Andrea, Zetterberg, Henrik, Boyanapalli, Ramakrishna, Rohrer, Jonathan D., and Isaacs, Adrian M.
Abstract: Objective A GGGGCC repeat expansion in the C9orf72 gene is the most common cause of genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). As potential therapies targeting the repeat expansion are now entering clinical trials, sensitive biomarker assays of target engagement are urgently required. Our objective was to develop such an assay. Methods We used the single molecule array (Simoa) platform to develop an immunoassay for measuring poly(GP) dipeptide repeat proteins (DPRs) generated by the C9orf72 repeat expansion in cerebrospinal fluid (CSF) of people with C9orf72-associated FTD/ALS. Results and conclusions We show the assay to be highly sensitive and robust, passing extensive qualification criteria including low intraplate and interplate variability, a high precision and accuracy in measuring both calibrators and samples, dilutional parallelism, tolerance to sample and standard freeze-thaw and no haemoglobin interference. We used this assay to measure poly(GP) in CSF samples collected through the Genetic FTD Initiative (N=40 C9orf72 and 15 controls). We found it had 100% specificity and 100% sensitivity and a large window for detecting target engagement, as the C9orf72 CSF sample with the lowest poly(GP) signal had eightfold higher signal than controls and on average values from C9orf72 samples were 38-fold higher than controls, which all fell below the lower limit of quantification of the assay. These data indicate that a Simoa-based poly(GP) DPR assay is suitable for use in clinical trials to determine target engagement of therapeutics aimed at reducing C9orf72 repeat-containing transcripts.
Published: 2022

32. Elevated CSF and plasma complement proteins in genetic frontotemporal dementia:results from the GENFI study

Author: van der Ende, Emma L., Heller, Carolin, Sogorb-Esteve, Aitana, Swift, Imogen J., McFall, David, Peakman, Georgia, Bouzigues, Arabella, Poos, Jackie M., Jiskoot, Lize C., Panman, Jessica L., Papma, Janne M., Meeter, Lieke H., Dopper, Elise G.P., Bocchetta, Martina, Todd, Emily, Cash, David, Graff, Caroline, Synofzik, Matthis, Moreno, Fermin, Finger, Elizabeth, Sanchez-Valle, Raquel, Vandenberghe, Rik, Laforce, Robert, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B., Butler, Chris, Ducharme, Simon, Gerhard, Alexander, Danek, Adrian, Levin, Johannes, Pijnenburg, Yolande A.L., Otto, Markus, Borroni, Barbara, Tagliavini, Fabrizio, de Mendonça, Alexandre, Santana, Isabel, Galimberti, Daniela, Sorbi, Sandro, Zetterberg, Henrik, Huang, Eric, van Swieten, John C., Rohrer, Jonathan D., Seelaar, Harro, van der Ende, Emma L., Heller, Carolin, Sogorb-Esteve, Aitana, Swift, Imogen J., McFall, David, Peakman, Georgia, Bouzigues, Arabella, Poos, Jackie M., Jiskoot, Lize C., Panman, Jessica L., Papma, Janne M., Meeter, Lieke H., Dopper, Elise G.P., Bocchetta, Martina, Todd, Emily, Cash, David, Graff, Caroline, Synofzik, Matthis, Moreno, Fermin, Finger, Elizabeth, Sanchez-Valle, Raquel, Vandenberghe, Rik, Laforce, Robert, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B., Butler, Chris, Ducharme, Simon, Gerhard, Alexander, Danek, Adrian, Levin, Johannes, Pijnenburg, Yolande A.L., Otto, Markus, Borroni, Barbara, Tagliavini, Fabrizio, de Mendonça, Alexandre, Santana, Isabel, Galimberti, Daniela, Sorbi, Sandro, Zetterberg, Henrik, Huang, Eric, van Swieten, John C., Rohrer, Jonathan D., and Seelaar, Harro
Abstract: BACKGROUND: Neuroinflammation is emerging as an important pathological process in frontotemporal dementia (FTD), but biomarkers are lacking. We aimed to determine the value of complement proteins, which are key components of innate immunity, as biomarkers in cerebrospinal fluid (CSF) and plasma of presymptomatic and symptomatic genetic FTD mutation carriers. METHODS: We measured the complement proteins C1q and C3b in CSF by ELISAs in 224 presymptomatic and symptomatic GRN, C9orf72 or MAPT mutation carriers and non-carriers participating in the Genetic Frontotemporal Dementia Initiative (GENFI), a multicentre cohort study. Next, we used multiplex immunoassays to measure a panel of 14 complement proteins in plasma of 431 GENFI participants. We correlated complement protein levels with corresponding clinical and neuroimaging data, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). RESULTS: CSF C1q and C3b, as well as plasma C2 and C3, were elevated in symptomatic mutation carriers compared to presymptomatic carriers and non-carriers. In genetic subgroup analyses, these differences remained statistically significant for C9orf72 mutation carriers. In presymptomatic carriers, several complement proteins correlated negatively with grey matter volume of FTD-related regions and positively with NfL and GFAP. In symptomatic carriers, correlations were additionally observed with disease duration and with Mini Mental State Examination and Clinical Dementia Rating scale® plus NACC Frontotemporal lobar degeneration sum of boxes scores. CONCLUSIONS: Elevated levels of CSF C1q and C3b, as well as plasma C2 and C3, demonstrate the presence of complement activation in the symptomatic stage of genetic FTD. Intriguingly, correlations with several disease measures in presymptomatic carriers suggest that complement protein levels might increase before symptom onset. Although the overlap between groups precludes their use as diagnosti
Published: 2022

33. CSF glial markers are elevated in a subset of patients with genetic frontotemporal dementia

Author: Woollacott, Ione O.C., Swift, Imogen J., Sogorb-Esteve, Aitana, Heller, Carolin, Knowles, Kathryn, Bouzigues, Arabella, Russell, Lucy L., Peakman, Georgia, Greaves, Caroline V., Convery, Rhian, Heslegrave, Amanda, Rowe, James B., Borroni, Barbara, Galimberti, Daniela, Tiraboschi, Pietro, Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, van Swieten, John C., Seelaar, Harro, Jiskoot, Lize, Sorbi, Sandro, Butler, Chris R., Graff, Caroline, Gerhard, Alexander, Laforce, Robert, Sanchez-Valle, Raquel, de Mendonça, Alexandre, Moreno, Fermin, Synofzik, Matthis, Vandenberghe, Rik, Ducharme, Simon, Ber, Isabelle Le, Levin, Johannes, Otto, Markus, Pasquier, Florence, Santana, Isabel, Zetterberg, Henrik, Rohrer, Jonathan D., Woollacott, Ione O.C., Swift, Imogen J., Sogorb-Esteve, Aitana, Heller, Carolin, Knowles, Kathryn, Bouzigues, Arabella, Russell, Lucy L., Peakman, Georgia, Greaves, Caroline V., Convery, Rhian, Heslegrave, Amanda, Rowe, James B., Borroni, Barbara, Galimberti, Daniela, Tiraboschi, Pietro, Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, van Swieten, John C., Seelaar, Harro, Jiskoot, Lize, Sorbi, Sandro, Butler, Chris R., Graff, Caroline, Gerhard, Alexander, Laforce, Robert, Sanchez-Valle, Raquel, de Mendonça, Alexandre, Moreno, Fermin, Synofzik, Matthis, Vandenberghe, Rik, Ducharme, Simon, Ber, Isabelle Le, Levin, Johannes, Otto, Markus, Pasquier, Florence, Santana, Isabel, Zetterberg, Henrik, and Rohrer, Jonathan D.
Abstract: Background: Neuroinflammation has been shown to be an important pathophysiological disease mechanism in frontotemporal dementia (FTD). This includes activation of microglia, a process that can be measured in life through assaying different glia-derived biomarkers in cerebrospinal fluid. However, only a few studies so far have taken place in FTD, and even fewer focusing on the genetic forms of FTD. Methods: We investigated the cerebrospinal fluid concentrations of TREM2, YKL-40 and chitotriosidase using immunoassays in 183 participants from the Genetic FTD Initiative (GENFI) study: 49 C9orf72 (36 presymptomatic, 13 symptomatic), 49 GRN (37 presymptomatic, 12 symptomatic) and 23 MAPT (16 presymptomatic, 7 symptomatic) mutation carriers and 62 mutation-negative controls. Concentrations were compared between groups using a linear regression model adjusting for age and sex, with 95% bias-corrected bootstrapped confidence intervals. Concentrations in each group were correlated with the Mini-Mental State Examination (MMSE) score using non-parametric partial correlations adjusting for age. Age-adjusted z-scores were also created for the concentration of markers in each participant, investigating how many had a value above the 95th percentile of controls. Results: Only chitotriosidase in symptomatic GRN mutation carriers had a concentration significantly higher than controls. No group had higher TREM2 or YKL-40 concentrations than controls after adjusting for age and sex. There was a significant negative correlation of chitotriosidase concentration with MMSE in presymptomatic GRN mutation carriers. In the symptomatic groups, for TREM2 31% of C9orf72, 25% of GRN, and 14% of MAPT mutation carriers had a concentration above the 95th percentile of controls. For YKL-40 this was 8% C9orf72, 8% GRN and 0% MAPT mutation carriers, whilst for chitotriosidase it was 23% C9orf72, 50% GRN, and 29% MAPT mutation carriers. Conclusions: Although chitotriosidase concentrations
Published: 2022

34. Development of a sensitive trial-ready poly(GP) CSF biomarker assay forC9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis

Author: Wilson, Katherine M, primary, Katona, Eszter, additional, Glaria, Idoia, additional, Carcolé, Mireia, additional, Swift, Imogen J, additional, Sogorb-Esteve, Aitana, additional, Heller, Carolin, additional, Bouzigues, Arabella, additional, Heslegrave, Amanda J, additional, Keshavan, Ashvini, additional, Knowles, Kathryn, additional, Patil, Saurabh, additional, Mohapatra, Susovan, additional, Liu, Yuanjing, additional, Goyal, Jaya, additional, Sanchez-Valle, Raquel, additional, Laforce, Robert Jr, additional, Synofzik, Matthis, additional, Rowe, James B, additional, Finger, Elizabeth, additional, Vandenberghe, Rik, additional, Butler, Christopher R, additional, Gerhard, Alexander, additional, Van Swieten, John C, additional, Seelaar, Harro, additional, Borroni, Barbara, additional, Galimberti, Daniela, additional, de Mendonça, Alexandre, additional, Masellis, Mario, additional, Tartaglia, M Carmela, additional, Otto, Markus, additional, Graff, Caroline, additional, Ducharme, Simon, additional, Schott, Jonathan M, additional, Malaspina, Andrea, additional, Zetterberg, Henrik, additional, Boyanapalli, Ramakrishna, additional, Rohrer, Jonathan D, additional, and Isaacs, Adrian M, additional
Published: 2022
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35. Differential Impairment Of Cerebrospinal Fluid Synaptic Biomarkers In The Genetic Forms Of Frontotemporal Dementia

Author: Sogorb-Esteve, Aitana, primary, Nilsson, Johanna, additional, Swift, Imogen J, additional, Heller, Carolin, additional, Russell, Lucy L., additional, Peakman, Georgia, additional, Convery, Rhian S., additional, Swieten, John C. van, additional, Seelaar, Harro, additional, Borroni, Barbara, additional, Galimberti, Daniela, additional, Sanchez-Valle, Raquel, additional, Laforce, Robert, additional, Moreno, Fermin, additional, Synofzik, Matthis, additional, Graff, Caroline, additional, Masellis, Mario, additional, Tartaglia, Maria Carmela, additional, Rowe, James B., additional, Vandenberghe, Rik, additional, Finger, Elizabeth, additional, Tagliavini, Fabrizio, additional, Santana, Isabel, additional, Butler, Chris R., additional, Ducharme, Simon, additional, Gerhard, Alexander, additional, Danek, Adrian, additional, Levin, Johannes, additional, Otto, Markus, additional, Sorbi, Sandro, additional, Ber, Isabelle Le, additional, Pasquier, Florence, additional, Gobom, Johan, additional, Brinkmalm, Ann, additional, Blennow, Kaj, additional, Zetterberg, Henrik, additional, and Rohrer, Jonathan D, additional
Published: 2022
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36. Network structure and transcriptomic vulnerability shape atrophy in frontotemporal dementia

Author: Shafiei, Golia, Bazinet, Vincent, Dadar, Mahsa, Manera, Ana L., Collins, D. Louis, Dagher, Alain, Borroni, Barbara, Sanchez-Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Synofzik, Matthis, Galimberti, Daniela, Rowe, James B., Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, Vandenberghe, Rik, de Mendonça, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Butler, Chris, Gerhard, Alex, Danek, Adrian, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Jiskoot, Lize C., Seelaar, Harro, van Swieten, John C., Rohrer, Jonathan D., Misic, Bratislav, Ducharme, Simon, Rosen, Howard, Dickerson, Bradford C., Domoto-Reilly, Kimoko, Knopman, David, Boeve, Bradley F., Boxer, Adam L., Kornak, John, Miller, Bruce L., Seeley, William W., Gorno-Tempini, Maria-Luisa, McGinnis, Scott, Mandelli, Maria Luisa, 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, van Der Ende, Emma, 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, 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, Fede, Giuseppe Di, do Couto, Frederico Simões, Shafiei, Golia [0000-0002-2036-5571], Dadar, Mahsa [0000-0003-4008-2672], Collins, D Louis [0000-0002-8432-7021], Dagher, Alain [0000-0002-0945-5779], Sanchez-Valle, Raquel [0000-0001-7750-896X], Graff, Caroline [0000-0002-9949-2951], Synofzik, Matthis [0000-0002-2280-7273], Masellis, Mario [0000-0002-6244-2096], Jiskoot, Lize C [0000-0002-8120-7366], Seelaar, Harro [0000-0003-1989-7527], Misic, Bratislav [0000-0003-0307-2862], Ducharme, Simon [0000-0002-7309-1113], and Apollo - University of Cambridge Repository
Subjects: Aging, connectome, disease epicentre, frontotemporal dementia, gene expression, network spreading, GENetic Frontotemporal dementia Initiative, Medizin, Neurodegenerative, Neuropsychological Tests, Alzheimer's Disease, diagnostic imaging [Frontotemporal Dementia], Medical and Health Sciences, Pick Disease of the Brain, Settore BIO/13 - Biologia Applicata, pathology [Brain], Frontotemporal Lobar Degeneration Neuroimaging Initiative, Acquired Cognitive Impairment, Connectome, 2.1 Biological and endogenous factors, Humans, ddc:610, Aetiology, genetics [Frontotemporal Dementia], pathology [Atrophy], Neurology & Neurosurgery, Psychology and Cognitive Sciences, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain, Magnetic Resonance Imaging, Brain Disorders, Frontotemporal Dementia (FTD), pathology [Pick Disease of the Brain], Neurological, pathology [Frontotemporal Dementia], Dementia, Neurology (clinical), Atrophy, Transcriptome
Abstract: Copyright © The Author(s) 2022. Connections among brain regions allow pathological perturbations to spread from a single source region to multiple regions. Patterns of neurodegeneration in multiple diseases, including behavioural variant of frontotemporal dementia (bvFTD), resemble the large-scale functional systems, but how bvFTD-related atrophy patterns relate to structural network organization remains unknown. Here we investigate whether neurodegeneration patterns in sporadic and genetic bvFTD are conditioned by connectome architecture. Regional atrophy patterns were estimated in both genetic bvFTD (75 patients, 247 controls) and sporadic bvFTD (70 patients, 123 controls). First, we identified distributed atrophy patterns in bvFTD, mainly targeting areas associated with the limbic intrinsic network and insular cytoarchitectonic class. Regional atrophy was significantly correlated with atrophy of structurally- and functionally-connected neighbours, demonstrating that network structure shapes atrophy patterns. The anterior insula was identified as the predominant group epicentre of brain atrophy using data-driven and simulation-based methods, with some secondary regions in frontal ventromedial and antero-medial temporal areas. We found that FTD-related genes, namely C9orf72 and TARDBP, confer local transcriptomic vulnerability to the disease, modulating the propagation of pathology through the connectome. Collectively, our results demonstrate that atrophy patterns in sporadic and genetic bvFTD are jointly shaped by global connectome architecture and local transcriptomic vulnerability, providing an explanation as to how heterogenous pathological entities can lead to the same clinical syndrome. Canada First Research Excellence Fund, awarded to McGill University for the Healthy Brains for Healthy Lives initiative. B.M. acknowledges support from the Natural Sciences and Engineering Research Council of Canada (NSERC Discovery Grant RGPIN #017-04265) and from the Canada Research Chairs Program. S.D. receives salary support from the Fonds de Recherche du Québec—Santé (FRQS). G.S. acknowledges support from the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Fonds de recherche du Québec—Nature et Technologies (FRQNT). V.B. acknowledges support from the Fonds de recherche du Québec—Nature et Technologies (FRQNT). FTLDNI data collection and sharing was funded by the Frontotemporal Lobar Degeneration Neuroimaging Initiative (National Institutes of Health Grant R01 AG032306) and is coordinated through the University of California, San Francisco, Memory and Aging Center. FTLDNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.
Published: 2022
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37. CSF glial markers are elevated in a subset of patients with genetic frontotemporal dementia

Author: Woollacott, Ione O C, Swift, Imogen J, Heslegrave, Amanda, Bargalló, Nuria, Borrego-Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B, Miltenberger, Gabriel, do Couto, Frederico Simões, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Rowe, James B, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Borroni, Barbara, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Galimberti, Daniela, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Tiraboschi, Pietro, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Masellis, Mario, Tábuas-Pereira, Miguel, Afonso, Sónia, Tartaglia, Maria Carmela, Finger, Elizabeth, van Swieten, John C, Seelaar, Harro, Sogorb-Esteve, Aitana, Jiskoot, Lize, Sorbi, Sandro, Butler, Chris R, Graff, Caroline, Gerhard, Alexander, Laforce, Robert, Sanchez-Valle, Raquel, de Mendonça, Alexandre, Moreno, Fermin, Synofzik, Matthis, Heller, Carolin, Vandenberghe, Rik, Ducharme, Simon, Ber, Isabelle Le, Levin, Johannes, Otto, Markus, Pasquier, Florence, Santana, Isabel, Zetterberg, Henrik, Rohrer, Jonathan D, Genetic FTD Initiative, GENFI, Knowles, Kathryn, Nelson, Annabel, Bocchetta, Martina, Cash, David, Thomas, David L, Todd, Emily, Benotmane, Hanya, Nicholas, Jennifer, Samra, Kiran, Shafei, Rachelle, Timberlake, Carolyn, Bouzigues, Arabella, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Russell, Lucy L, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Peakman, Georgia, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Greaves, Caroline V, Papma, Janne M, Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Convery, Rhian, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Genetic FTD Initiative, GENFI, Russell, Lucy L [0000-0001-5023-5893], Borroni, Barbara [0000-0001-9340-9814], Galimberti, Daniela [0000-0002-9284-5953], Tiraboschi, Pietro [0000-0002-2171-1720], Tartaglia, Maria Carmela [0000-0002-5944-8497], Finger, Elizabeth [0000-0003-4461-7427], Laforce, Robert [0000-0002-2031-490X], Sanchez-Valle, Raquel [0000-0001-7750-896X], Synofzik, Matthis [0000-0002-2280-7273], Ducharme, Simon [0000-0002-7309-1113], Otto, Markus [0000-0003-4273-4267], Rohrer, Jonathan D [0000-0002-6155-8417], Apollo - University of Cambridge Repository, Repositório da Universidade de Lisboa, Neurology, Clinical Genetics, and Amsterdam Neuroscience - Neurodegeneration
Subjects: C9orf72 Protein, General Neuroscience, Medizin, diagnosis [Frontotemporal Dementia], cerebrospinal fluid [Biomarkers], Pick Disease of the Brain, Settore BIO/13 - Biologia Applicata, Frontotemporal Dementia, genetics [Chitinase-3-Like Protein 1], Humans, ddc:610, Chitinase-3-Like Protein 1, Human medicine, Neurology (clinical), genetics [C9orf72 Protein], Neuroglia, Biomarkers
Abstract: Funder: Alzheimer's Research UK, Funder: Brain Research UK; Id: http://dx.doi.org/10.13039/100013790, Funder: The Wolfson Foundation; Id: http://dx.doi.org/10.13039/501100001320, Funder: Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, Funder: UK Dementia Research Institute; Id: http://dx.doi.org/10.13039/501100017510, Funder: UK DRI Ltd; Id: http://dx.doi.org/10.13039/501100017510, Funder: MRC UK GENFI, Funder: Bluefield Project, Funder: Dioraphte Foundation; Id: http://dx.doi.org/10.13039/501100010573, Funder: Weston Brain Institute; Id: http://dx.doi.org/10.13039/100012479, Funder: Ontario Brain Institute; Id: http://dx.doi.org/10.13039/100008914, Funder: Cambridge University Centre for Frontotemporal Dementia, Funder: EU Joint Programme – Neurodegenerative Disease Research; Id: http://dx.doi.org/10.13039/100013278, Funder: the Olav Thon Foundation; Id: http://dx.doi.org/10.13039/501100021720, Funder: Erling‐Persson Family Foundation; Id: http://dx.doi.org/10.13039/100007436, Funder: Stiftelsen för Gamla Tjänarinnor; Id: http://dx.doi.org/10.13039/100010815, Funder: Deutsche Forschungsgemeinschaft; Id: http://dx.doi.org/10.13039/501100001659, BACKGROUND: Neuroinflammation has been shown to be an important pathophysiological disease mechanism in frontotemporal dementia (FTD). This includes activation of microglia, a process that can be measured in life through assaying different glia-derived biomarkers in cerebrospinal fluid. However, only a few studies so far have taken place in FTD, and even fewer focusing on the genetic forms of FTD. METHODS: We investigated the cerebrospinal fluid concentrations of TREM2, YKL-40 and chitotriosidase using immunoassays in 183 participants from the Genetic FTD Initiative (GENFI) study: 49 C9orf72 (36 presymptomatic, 13 symptomatic), 49 GRN (37 presymptomatic, 12 symptomatic) and 23 MAPT (16 presymptomatic, 7 symptomatic) mutation carriers and 62 mutation-negative controls. Concentrations were compared between groups using a linear regression model adjusting for age and sex, with 95% bias-corrected bootstrapped confidence intervals. Concentrations in each group were correlated with the Mini-Mental State Examination (MMSE) score using non-parametric partial correlations adjusting for age. Age-adjusted z-scores were also created for the concentration of markers in each participant, investigating how many had a value above the 95th percentile of controls. RESULTS: Only chitotriosidase in symptomatic GRN mutation carriers had a concentration significantly higher than controls. No group had higher TREM2 or YKL-40 concentrations than controls after adjusting for age and sex. There was a significant negative correlation of chitotriosidase concentration with MMSE in presymptomatic GRN mutation carriers. In the symptomatic groups, for TREM2 31% of C9orf72, 25% of GRN, and 14% of MAPT mutation carriers had a concentration above the 95th percentile of controls. For YKL-40 this was 8% C9orf72, 8% GRN and 0% MAPT mutation carriers, whilst for chitotriosidase it was 23% C9orf72, 50% GRN, and 29% MAPT mutation carriers. CONCLUSIONS: Although chitotriosidase concentrations in GRN mutation carriers were the only significantly raised glia-derived biomarker as a group, a subset of mutation carriers in all three groups, particularly for chitotriosidase and TREM2, had elevated concentrations. Further work is required to understand the variability in concentrations and the extent of neuroinflammation across the genetic forms of FTD. However, the current findings suggest limited utility of these measures in forthcoming trials.
Published: 2022
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38. Additional file 2 of Differential impairment of cerebrospinal fluid synaptic biomarkers in the genetic forms of frontotemporal dementia

Author: Sogorb-Esteve, Aitana, Nilsson, Johanna, Swift, Imogen J., Heller, Carolin, Bocchetta, Martina, Russell, Lucy L., Peakman, Georgia, Convery, Rhian S., van Swieten, John 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, Santana, Isabel, Butler, Chris R., Ducharme, Simon, Gerhard, Alexander, Danek, Adrian, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Le Ber, Isabelle, Pasquier, Florence, Gobom, Johan, Brinkmalm, Ann, Blennow, Kaj, Zetterberg, Henrik, and Rohrer, Jonathan D.
Abstract: Additional file 2: Appendix 1. List of GENFI consortium authors.
Published: 2022
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39. Additional file 1 of Elevated CSF and plasma complement proteins in genetic frontotemporal dementia: results from the GENFI study

Author: van der Ende, Emma L., Heller, Carolin, Sogorb-Esteve, Aitana, Swift, Imogen J., McFall, David, Peakman, Georgia, Bouzigues, Arabella, Poos, Jackie M., Jiskoot, Lize C., Panman, Jessica L., Papma, Janne M., Meeter, Lieke H., Dopper, Elise G. P., Bocchetta, Martina, Todd, Emily, Cash, David, Graff, Caroline, Synofzik, Matthis, Moreno, Fermin, Finger, Elizabeth, Sanchez-Valle, Raquel, Vandenberghe, Rik, Laforce, Robert, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B., Butler, Chris, Ducharme, Simon, Gerhard, Alexander, Danek, Adrian, Levin, Johannes, Pijnenburg, Yolande A. L., Otto, Markus, Borroni, Barbara, Tagliavini, Fabrizio, de Mendonça, Alexandre, Santana, Isabel, Galimberti, Daniela, Sorbi, Sandro, Zetterberg, Henrik, Huang, Eric, van Swieten, John C., Rohrer, Jonathan D., and Seelaar, Harro
Abstract: Additional file 1: Table S1. Number of samples for each of the analytes in CSF and plasma. Table S2. Correlations between complement proteins and age. Table S3. Correlations between grey matter volume and (a) CSF and (b) plasma complement protein concentration. Table S4. Correlations between clinical measures of disease severity and (a) CSF and (b) plasma complement proteins. Table S5. Correlations between plasma complement factors. Table S6. Correlations between plasma complement proteins, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). Table S7. Complement protein levels of seven presymptomatic carriers who became symptomatic during follow-up (‘converters’). Figure S1. Correlations between CSF C1q, C3b and disease duration. P-values were derived from Spearman’s rho.
Published: 2022
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40. Additional file 3 of Differential impairment of cerebrospinal fluid synaptic biomarkers in the genetic forms of frontotemporal dementia

Author: Sogorb-Esteve, Aitana, Nilsson, Johanna, Swift, Imogen J., Heller, Carolin, Bocchetta, Martina, Russell, Lucy L., Peakman, Georgia, Convery, Rhian S., van Swieten, John 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, Santana, Isabel, Butler, Chris R., Ducharme, Simon, Gerhard, Alexander, Danek, Adrian, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Le Ber, Isabelle, Pasquier, Florence, Gobom, Johan, Brinkmalm, Ann, Blennow, Kaj, Zetterberg, Henrik, and Rohrer, Jonathan D.
Abstract: Additional file 3: Appendix 2. IS preparation and LC-MS settings for theanalysis of the synaptic protein panel.
Published: 2022
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41. Additional file 1 of Differential impairment of cerebrospinal fluid synaptic biomarkers in the genetic forms of frontotemporal dementia

Author: Sogorb-Esteve, Aitana, Nilsson, Johanna, Swift, Imogen J., Heller, Carolin, Bocchetta, Martina, Russell, Lucy L., Peakman, Georgia, Convery, Rhian S., van Swieten, John 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, Santana, Isabel, Butler, Chris R., Ducharme, Simon, Gerhard, Alexander, Danek, Adrian, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Le Ber, Isabelle, Pasquier, Florence, Gobom, Johan, Brinkmalm, Ann, Blennow, Kaj, Zetterberg, Henrik, and Rohrer, Jonathan D.
Abstract: Additional file 1: Supplementary tables.
Published: 2022
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42. Development of a sensitive trial-ready poly(GP) CSF biomarker assay for C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis

Author: Wilson, Katherine M, primary, Katona, Eszter, additional, Glaria, Idoia, additional, Swift, Imogen J., additional, Sogorb-Esteve, Aitana, additional, Heller, Carolin, additional, Bouzigues, Arabella, additional, Heslegrave, Amanda J, additional, Patil, Saurabh, additional, Mohapatra, Susovan, additional, Liu, Yuanjing, additional, Goyal, Jaya, additional, Sanchez-Valle, Raquel, additional, Laforce, Robert, additional, Synofzik, Matthis, additional, Rowe, James B., additional, Finger, Elizabeth, additional, Vandenberghe, Rik, additional, Butler, Chris R., additional, Gerhard, Alexander, additional, van Swieten, John, additional, Seelaar, Harro, additional, Borroni, Barbara, additional, Galimberti, Daniela, additional, Mendonça, Alexandre de, additional, Masellis, Mario, additional, Tartaglia, Carmela, additional, Otto, Markus, additional, Graff, Caroline, additional, Ducharme, Simon, additional, Malaspina, Andrea, additional, Zetterberg, Henrik, additional, Boyanapalli, Ramakrishna, additional, Rohrer, Jonathan D, additional, and Isaacs, Adrian M, additional
Published: 2021
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43. A data‐driven disease progression model of fluid biomarkers in genetic FTD

Author: van der Ende, Emma, primary, Bron, Esther E., additional, Poos, Jackie M., additional, Jiskoot, Lize C., additional, Panman, Jessica L., additional, Papma, Janne M., additional, Wilke, Carlo, additional, Synofzik, Matthis, additional, Heller, Carolin, additional, Swift, Imogen J., additional, Esteve, Aitana Sogorb, additional, Bouzigues, Arabella, additional, Borroni, Barbara, additional, Sanchez‐Valle, Raquel, additional, Moreno, Fermin, additional, Graff, Caroline, additional, Laforce, Robert, additional, Galimberti, Daniela, additional, Masellis, Mario, additional, Tartaglia, Maria Carmela, additional, Finger, Elizabeth, additional, Vandenberghe, Rik, additional, Rowe, James B., additional, Mendonca, Alexandre, additional, Tagliavini, Fabrizio, additional, Santana, Isabel, additional, Ducharme, Simon, additional, Butler, Christopher, additional, Gerhard, Alexander, additional, Levin, Johannes, additional, Danek, Adrian, additional, Otto, Markus, additional, Pijnenburg, Yolande A.L., additional, Frisoni, Giovanni B., additional, Sorbi, Sandro, additional, Ghidoni, Roberta, additional, Niessen, Wiro J., additional, Rohrer, Jonathan D., additional, Klein, Stefan, additional, van Swieten, John C, additional, Venkatraghavan, Vikram, additional, and Seelaar, Harro, additional
Published: 2021
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44. A systematic review of progranulin concentrations in biofluids in over 7,000 people: Assessing the pathogenicity of GRN mutations and other influencing factors

Author: Swift, Imogen J., primary, Esteve, Aitana Sogorb, additional, Heller, Carolin, additional, Zetterberg, Henrik, additional, and Rohrer, Jonathan D., additional
Published: 2021
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45. Additional file 2 of Differential chemokine alteration in the variants of primary progressive aphasia—a role for neuroinflammation

Author: Sogorb-Esteve, Aitana, Swift, Imogen J., Woollacott, Ione O. C., Warren, Jason D., Zetterberg, Henrik, and Rohrer, Jonathan D.
Subjects: respiratory system
Abstract: Additional file 2: Supplementary Table 1. Spearman correlation coefficients and p-values comparing chemokines with age at CSF collection within the control group. Supplementary Table 2. Mean (standard deviation) normalized protein expression values for the chemokines in controls and each of PPA groups in CSF. Mean differences between the PPA groups and controls along with 95% confidence intervals and p values (significant in bold) are shown underneath. N/A = not assessed >80% values were below the lower limit of detection. Supplementary Table 3. Mean (standard deviation) normalized protein expression values for the chemokines in controls and each of PPA groups in plasma. Mean differences between the PPA groups and controls along with 95% confidence intervals and p values (significant in bold) are shown underneath. N/A = not assessed >80% values were below the lower limit of detection.
Published: 2021
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46. Impairment of episodic memory in genetic frontotemporal dementia

Author: Poos, Jackie M, Russell, Lucy L, Pijnenburg, Yolande A L, Bender, Benjamin, Bruffaerts, Rose, Vandamme, Philip, Vandenbulcke, Mathieu, Ferreira, Catarina B, Miltenberger, Gabriel, Maruta, Carolina, Verdelho, Ana, Afonso, Sónia, Taipa, Ricardo, Borroni, Barbara, Caroppo, Paola, Di Fede, Giuseppe, Giaccone, Giorgio, Prioni, Sara, Redaelli, Veronica, Rossi, Giacomina, Tiraboschi, Pietro, Duro, Diana, Almeida, Maria Rosario, Castelo-Branco, Miguel, Sanchez-Valle, Raquel, Leitão, Maria João, Tabuas-Pereira, Miguel, Santiago, Beatriz, Gauthier, Serge, Rosa-Neto, Pedro, Veldsman, Michele, Thompson, Paul, Langheinrich, Tobias, Prix, Catharina, Hoegen, Tobias, Moreno, Fermin, Wlasich, Elisabeth, Loosli, Sandra, Schonecker, Sonja, Anderl-Straub, Sarah, Lombardi, Jolina, Bargalló, Nuria, Benussi, Alberto, Cantoni, Valentina, Bertoux, Maxime, Bertrand, Anne, Laforce, Robert, Brice, Alexis, Camuzat, Agnès, Colliot, Olivier, Sayah, Sabrina, Funkiewiez, Aurélie, Rinaldi, Daisy, Lombardi, Gemma, Nacmias, Benedetta, Saracino, Dario, Bessi, Valentina, Graff, Caroline, Ferrari, Camilla, Cañada, Marta, Deramecourt, Vincent, Kuchcinski, Gregory, Lebouvier, Thibaud, Ourselin, Sebastien, Polito, Cristina, Rollin, Adeline, Synofzik, Matthias, Galimberti, Daniela, Rowe, James B, Masellis, Mario, Peakman, Georgia, Tartaglia, Carmela, Finger, Elizabeth, Vandenberghe, Rik, de Medonça, Alexandre, Tagliavini, Fabrizio, Butler, Chris R, Santana, Isabel, Ber, Isabelle Le, Gerhard, Alex, Ducharme, Simon, Bocchetta, Martina, Levin, Johannes, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Pasquier, Florence, van Swieten, John C, Rohrer, Jonathan D, Genetic FTD Initiative, GENF, Rossor, Martin N, Fox, Nick C, Greaves, Caroline V, Warren, Jason D, Moore, Katrina, Convery, Rhian, Swift, Imogen J, Shafei, Rachelle, Heller, Carolin, Todd, Emily, Bouzigues, Arabella, Cash, David, Woollacott, Ione, Jiskoot, Lize C, Zetterberg, Henrik, Nelson, Annabel, Nicholas, Jennifer, Guerreiro, Rita, Bras, Jose, Thomas, David L, Mead, Simon, Meeter, Lieke, Panman, Jessica, van Minkelen, Rick, van der Ende, Emma L, Barandiaran, Myriam, Indakoetxea, Begoña, Gabilondo, Alazne, Tainta, Mikel, Gorostidi, Ana, Zulaica, Miren, Díez, Alina, Villanua, Jorge, Borrego-Ecija, Sergi, Jaume, Olives, Seelaar, Harro, Lladó, Albert, Balasa, Mircea, Antonell, Anna, Bargallo, Nuria, Premi, Enrico, Gazzina, Stefano, Gasparotti, Roberto, Archetti, Silvana, Black, Sandra, Mitchell, Sara, Papma, Janne M, Rogaeva, Ekaterina, Freedman, Morris, Keren, Ron, Tang-Wai, David, Thonberg, Hakan, Öijerstedt, Linn, Andersson, Christin, Jelic, Vesna, Arighi, Andrea, Fenoglio, Chiara, van den Berg, Esther, Scarpini, Elio, Fumagalli, Giorgio, Cope, Thomas, Timberlake, Carolyn, Rittman, Timothy, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Wilke, Carlo, Karnarth, Hans-Otto, Apollo - University of Cambridge Repository, Repositório da Universidade de Lisboa, Rowe, James [0000-0001-7216-8679], Rowe, James B [0000-0001-7216-8679], Neurology, Amsterdam Neuroscience - Neurodegeneration, Genetic FTD Initiative, GENFI, Radiology & Nuclear Medicine, Neurosurgery, Clinical Psychology, and Clinical Genetics
Subjects: cognition, Medizin, neuropsychology, Audiology, frontotemporal dementia, DISEASE, 0302 clinical medicine, COGNITIVE & BEHAVIORAL ASSESSMENT, C9orf72, BEHAVIORAL VARIANT, CRITERIA, voxel‐based morphometry, ALZHEIMERS, Episodic memory, 0303 health sciences, episodic memory, CARRIERS, frontal lobe, Psychiatry and Mental health, Frontal lobe, Life Sciences & Biomedicine, Frontotemporal dementia, temporal lobe, Cognition, Executive function, Genetic disorders, Neuropsychology, Temporal lobe, Voxel-based morphometry, medicine.medical_specialty, Clinical Neurology, DIAGNOSIS, RESEARCH ARTICLE, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, Memory impairment, voxel-based morphometry, genetic disorders, ddc:610, PROGRANULIN, RC346-429, 030304 developmental biology, 0604 Genetics, Science & Technology, Recall, business.industry, RC952-954.6, Neurosciences, PROFILES, medicine.disease, executive function, Geriatrics, VOLUME, Genetic FTD Initiative, GENF, Neurology (clinical), Neurology. Diseases of the nervous system, Neurosciences & Neurology, business, 1109 Neurosciences, 030217 neurology & neurosurgery
Abstract: © 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring 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-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made., Introduction: We aimed to assess episodic memory in genetic frontotemporal dementia (FTD) with the Free and Cued Selective Reminding Test (FCSRT). Methods: The FCSRT was administered in 417 presymptomatic and symptomatic mutation carriers (181 chromosome 9 open reading frame 72 [C9orf72], 163 progranulin [GRN], and 73 microtubule-associated protein tau [MAPT]) and 290 controls. Group differences and correlations with other neuropsychological tests were examined. We performed voxel-based morphometry to investigate the underlying neural substrates of the FCSRT. Results: All symptomatic mutation carrier groups and presymptomatic MAPT mutation carriers performed significantly worse on all FCSRT scores compared to controls. In the presymptomatic C9orf72 group, deficits were found on all scores except for the delayed total recall task, while no deficits were found in presymptomatic GRN mutation carriers. Performance on the FCSRT correlated with executive function, particularly in C9orf72 mutation carriers, but also with memory and naming tasks in the MAPT group. FCSRT performance also correlated with gray matter volumes of frontal, temporal, and subcortical regions in C9orf72 and GRN, but mainly temporal areas in MAPT mutation carriers. Discussion: The FCSRT detects presymptomatic deficits in C9orf72- and MAPT-associated FTD and provides important insight into the underlying cause of memory impairment in different forms of FTD., 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 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. J. D. Rohrer 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; the JPND GENFI-PROX grant (2019-02248); the Dioraphte Foundation (grant numbers 09-02-00); the Association for Frontotemporal Dementias Research Grant 2009; The Netherlands Organization for Scientific Research (NWO; grant HCMI 056-13-018); ZonMw Memorabel (Deltaplan Dementie, project numbers 733 050 103 and 733 050 813); JPND PreFrontAls consortium (project number 733051042). J. M. Poos is supported by a Fellowship award from Alzheimer Nederland (WE.15-2019.02). This work was conducted using the MRC Dementias Platform UK (MR/L023784/1 and MR/009076/1). Several authors of this publication are members of the European Reference Network for Rare Neurological Diseases - Project ID No 739510.
Published: 2021
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47. Impairment of episodic memory in genetic frontotemporal dementia:A genfi study

Author: Poos, Jackie M., Russell, Lucy L., Peakman, Georgia, Bocchetta, Martina, Greaves, Caroline V., Jiskoot, Lize C., van der Ende, Emma L., Seelaar, Harro, Papma, Janne M., van den Berg, Esther, Pijnenburg, Yolande A.L., Borroni, Barbara, Sanchez-Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Synofzik, Matthias, Galimberti, Daniela, Rowe, James B., Masellis, Mario, Tartaglia, Carmela, Finger, Elizabeth, Vandenberghe, Rik, Medonça, Alexandre de, Tagliavini, Fabrizio, Butler, Chris R., Santana, Isabel, Ber, Isabelle Le, Gerhard, Alex, Ducharme, Simon, Levin, Johannes, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Pasquier, Florence, van Swieten, John C., Rohrer, Jonathan D., Rossor, Martin N., Fox, Nick C., Warren, Jason D., Moore, Katrina, Convery, Rhian, Swift, Imogen J., Shafei, Rachelle, Heller, Carolin, Todd, Emily, Bouzigues, Arabella, Cash, David, Woollacott, Ione, Zetterberg, Henrik, Nelson, Annabel, Nicholas, Jennifer, Guerreiro, Rita, Bras, Jose, Thomas, David L., Mead, Simon, Meeter, Lieke, Pan-Man, Jessica, Minkelen, Rick van, Barandiaran, Myriam, Indakoetxea, Begoña, Gabilondo, Alazne, Tainta, Mikel, Gorostidi, Ana, Zulaica, Miren, Díez, Alina, Vil-Lanua, Jorge, Borrego-Ecija, Sergi, Olives, Jaume, Lladó, Albert, Balasa, Mircea, Antonell, Anna, Bargalló, Nuria, Premi, Enrico, Gazzina, Stefano, Gasparotti, Roberto, Archetti, Silvana, Black, Sandra, Mitchell, Sara, Rogaeva, Ekaterina, Freedman, Morris, Keren, Ron, Tang-Wai, David, Thon-Berg, Hakan, Öijerstedt, Linn, Andersson, Christin, Jelic, Vesna, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Cope, Thomas, Timberlake, Carolyn, Rittman, Timothy, Shoe-Smith, Christen, Bartha, Robart, Rademakers, Rosa, Wilke, Carlo, Karnarth, Hans Otto, Bender, Benjamin, Bruffaerts, Rose, Vandamme, Philip, Vandenbulcke, Math Ieu, Ferreira, Catarina B., Miltenberger, Gabriel, Mpsych, Carolina Maruta, Verdelho, Ana, Afonso, Sónia, Taipa, Ricardo, Caroppo, Paola, Fede, Giuseppe Di, Giac-Cone, Giorgio, Prioni, Sara, Redaelli, Veronica, Rossi, Giacomina, Tiraboschi, Pietro, Duro, Diana, Almeida, Maria Rosario, Castelo-Branco, Miguel, Leitão, Maria João, Tabuas-Pereira, Miguel, Santiago, Beatriz, Gauthier, Serge, Rosa-Neto, Pedro, Velds-Man, Michele, Thompson, Paul, Langheinrich, Tobias, Prix, Catharina, Hoegen, Tobias, Wlasich, Elisabeth, Loosli, Sandra, Schonecker, Sonja, Anderl-Straub, Sarah, Lombardi, Jolina, Benussi, Alberto, Cantoni, Valentina, Bertoux, Maxime, Bertrand, Anne, Brice, Alexis, Camuzat, Agnès, Colliot, Olivier, Sayah, Sabrina, Funkiewiez, Aurélie, Rinaldi, Daisy, Lombardi, Gemma, Nacmias, Benedetta, Saracino, Dario, Bessi, Valentina, Ferrari, Camilla, Cañada, Marta, Deramecourt, Vincent, Kuchcinski, Gregory, Lebouvier, Thibaud, Ourselin, Sebastien, Polito, Cristina, Rollin, Adeline, Poos, Jackie M., Russell, Lucy L., Peakman, Georgia, Bocchetta, Martina, Greaves, Caroline V., Jiskoot, Lize C., van der Ende, Emma L., Seelaar, Harro, Papma, Janne M., van den Berg, Esther, Pijnenburg, Yolande A.L., Borroni, Barbara, Sanchez-Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Synofzik, Matthias, Galimberti, Daniela, Rowe, James B., Masellis, Mario, Tartaglia, Carmela, Finger, Elizabeth, Vandenberghe, Rik, Medonça, Alexandre de, Tagliavini, Fabrizio, Butler, Chris R., Santana, Isabel, Ber, Isabelle Le, Gerhard, Alex, Ducharme, Simon, Levin, Johannes, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Pasquier, Florence, van Swieten, John C., Rohrer, Jonathan D., Rossor, Martin N., Fox, Nick C., Warren, Jason D., Moore, Katrina, Convery, Rhian, Swift, Imogen J., Shafei, Rachelle, Heller, Carolin, Todd, Emily, Bouzigues, Arabella, Cash, David, Woollacott, Ione, Zetterberg, Henrik, Nelson, Annabel, Nicholas, Jennifer, Guerreiro, Rita, Bras, Jose, Thomas, David L., Mead, Simon, Meeter, Lieke, Pan-Man, Jessica, Minkelen, Rick van, Barandiaran, Myriam, Indakoetxea, Begoña, Gabilondo, Alazne, Tainta, Mikel, Gorostidi, Ana, Zulaica, Miren, Díez, Alina, Vil-Lanua, Jorge, Borrego-Ecija, Sergi, Olives, Jaume, Lladó, Albert, Balasa, Mircea, Antonell, Anna, Bargalló, Nuria, Premi, Enrico, Gazzina, Stefano, Gasparotti, Roberto, Archetti, Silvana, Black, Sandra, Mitchell, Sara, Rogaeva, Ekaterina, Freedman, Morris, Keren, Ron, Tang-Wai, David, Thon-Berg, Hakan, Öijerstedt, Linn, Andersson, Christin, Jelic, Vesna, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Cope, Thomas, Timberlake, Carolyn, Rittman, Timothy, Shoe-Smith, Christen, Bartha, Robart, Rademakers, Rosa, Wilke, Carlo, Karnarth, Hans Otto, Bender, Benjamin, Bruffaerts, Rose, Vandamme, Philip, Vandenbulcke, Math Ieu, Ferreira, Catarina B., Miltenberger, Gabriel, Mpsych, Carolina Maruta, Verdelho, Ana, Afonso, Sónia, Taipa, Ricardo, Caroppo, Paola, Fede, Giuseppe Di, Giac-Cone, Giorgio, Prioni, Sara, Redaelli, Veronica, Rossi, Giacomina, Tiraboschi, Pietro, Duro, Diana, Almeida, Maria Rosario, Castelo-Branco, Miguel, Leitão, Maria João, Tabuas-Pereira, Miguel, Santiago, Beatriz, Gauthier, Serge, Rosa-Neto, Pedro, Velds-Man, Michele, Thompson, Paul, Langheinrich, Tobias, Prix, Catharina, Hoegen, Tobias, Wlasich, Elisabeth, Loosli, Sandra, Schonecker, Sonja, Anderl-Straub, Sarah, Lombardi, Jolina, Benussi, Alberto, Cantoni, Valentina, Bertoux, Maxime, Bertrand, Anne, Brice, Alexis, Camuzat, Agnès, Colliot, Olivier, Sayah, Sabrina, Funkiewiez, Aurélie, Rinaldi, Daisy, Lombardi, Gemma, Nacmias, Benedetta, Saracino, Dario, Bessi, Valentina, Ferrari, Camilla, Cañada, Marta, Deramecourt, Vincent, Kuchcinski, Gregory, Lebouvier, Thibaud, Ourselin, Sebastien, Polito, Cristina, and Rollin, Adeline
Abstract: Introduction: We aimed to assess episodic memory in genetic frontotemporal dementia (FTD) with the Free and Cued Selective Reminding Test (FCSRT). Methods: The FCSRT was administered in 417 presymptomatic and symptomatic mutation carriers (181 chromosome 9 open reading frame 72 [C9orf72], 163 progran-ulin [GRN], and 73 microtubule-associated protein tau [MAPT]) and 290 controls. Group differences and correlations with other neuropsychological tests were examined. We performed voxel-based morphometry to investigate the underlying neural substrates of the FCSRT. Results: All symptomatic mutation carrier groups and presymptomatic MAPT mutation carriers performed significantly worse on all FCSRT scores compared to controls. In the presymptomatic C9orf72 group, deficits were found on all scores except for the delayed total recall task, while no deficits were found in presymptomatic GRN mutation carriers. Performance on the FCSRT correlated with executive function, particularly in C9orf72 mutation carriers, but also with memory and naming tasks in the MAPT group. FCSRT performance also correlated with gray matter volumes of frontal, temporal, and subcortical regions in C9orf72 and GRN, but mainly temporal areas in MAPT mutation carriers. Discussion: The FCSRT detects presymptomatic deficits in C9orf72-and MAPT-associated FTD and provides important insight into the underlying cause of memory impairment in different forms of FTD.
Published: 2021

48. Plasma amyloid-β ratios in autosomal dominant Alzheimer’s disease: the influence of genotype

Author: O'Connor, Antoinette, primary, Pannee, Josef, additional, Poole, Teresa, additional, Arber, Charles, additional, Portelius, Erik, additional, Swift, Imogen J, additional, Heslegrave, Amanda J, additional, Abel, Emily, additional, Willumsen, Nanet, additional, Rice, Helen, additional, Weston, Philip S J, additional, Ryan, Natalie S, additional, Polke, James M, additional, Nicholas, Jennifer M, additional, Mead, Simon, additional, Wray, Selina, additional, Chávez-Gutiérrez, Lucía, additional, Frost, Chris, additional, Blennow, Kaj, additional, Zetterberg, Henrik, additional, and Fox, Nick C, additional
Published: 2021
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49. Differential Chemokine Alteration in the Variants of Primary Progressive Aphasia – A Role for Neuroinflammation

Author: Esteve, Aitana Sogorb, primary, Swift, Imogen J., additional, Woollacott, Ione O.C., additional, Warren, Jason D., additional, Zetterberg, Henrik, additional, and Rohrer, Jonathan D., additional
Published: 2021
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50. A data-driven disease progression model of fluid biomarkers in genetic frontotemporal dementia.

Author: Ende, Emma L van der, Bron, Esther E, Poos, Jackie M, Jiskoot, Lize C, Panman, Jessica L, Papma, Janne M, Meeter, Lieke H, Dopper, Elise G P, Wilke, Carlo, Synofzik, Matthis, Heller, Carolin, Swift, Imogen J, Sogorb-Esteve, Aitana, Bouzigues, Arabella, Borroni, Barbara, Sanchez-Valle, Raquel, Moreno, Fermin, Graff, Caroline, Laforce, Robert, and Galimberti, Daniela
Subjects: DISEASE progression, RESEARCH, NERVE tissue proteins, COMPLEMENT (Immunology), GENETIC mutation, CROSS-sectional method, RESEARCH methodology, CYTOSKELETAL proteins, EVALUATION research, COMPARATIVE studies, RESEARCH funding, FRONTOTEMPORAL dementia, LONGITUDINAL method
Abstract: Several CSF and blood biomarkers for genetic frontotemporal dementia have been proposed, including those reflecting neuroaxonal loss (neurofilament light chain and phosphorylated neurofilament heavy chain), synapse dysfunction [neuronal pentraxin 2 (NPTX2)], astrogliosis (glial fibrillary acidic protein) and complement activation (C1q, C3b). Determining the sequence in which biomarkers become abnormal over the course of disease could facilitate disease staging and help identify mutation carriers with prodromal or early-stage frontotemporal dementia, which is especially important as pharmaceutical trials emerge. We aimed to model the sequence of biomarker abnormalities in presymptomatic and symptomatic genetic frontotemporal dementia using cross-sectional data from the Genetic Frontotemporal dementia Initiative (GENFI), a longitudinal cohort study. Two-hundred and seventy-five presymptomatic and 127 symptomatic carriers of mutations in GRN, C9orf72 or MAPT, as well as 247 non-carriers, were selected from the GENFI cohort based on availability of one or more of the aforementioned biomarkers. Nine presymptomatic carriers developed symptoms within 18 months of sample collection ('converters'). Sequences of biomarker abnormalities were modelled for the entire group using discriminative event-based modelling (DEBM) and for each genetic subgroup using co-initialized DEBM. These models estimate probabilistic biomarker abnormalities in a data-driven way and do not rely on previous diagnostic information or biomarker cut-off points. Using cross-validation, subjects were subsequently assigned a disease stage based on their position along the disease progression timeline. CSF NPTX2 was the first biomarker to become abnormal, followed by blood and CSF neurofilament light chain, blood phosphorylated neurofilament heavy chain, blood glial fibrillary acidic protein and finally CSF C3b and C1q. Biomarker orderings did not differ significantly between genetic subgroups, but more uncertainty was noted in the C9orf72 and MAPT groups than for GRN. Estimated disease stages could distinguish symptomatic from presymptomatic carriers and non-carriers with areas under the curve of 0.84 (95% confidence interval 0.80-0.89) and 0.90 (0.86-0.94) respectively. The areas under the curve to distinguish converters from non-converting presymptomatic carriers was 0.85 (0.75-0.95). Our data-driven model of genetic frontotemporal dementia revealed that NPTX2 and neurofilament light chain are the earliest to change among the selected biomarkers. Further research should investigate their utility as candidate selection tools for pharmaceutical trials. The model's ability to accurately estimate individual disease stages could improve patient stratification and track the efficacy of therapeutic interventions. [ABSTRACT FROM AUTHOR]
Published: 2022
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