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1. LATE-NC risk alleles (in TMEM106B, GRN, and ABCC9 genes) among persons with African ancestry.

Author: Katsumata, Yuriko, Fardo, David W, Shade, Lincoln MP, Bowen, James D, Crane, Paul K, Jarvik, Gail P, Keene, C Dirk, Larson, Eric B, McCormick, Wayne C, McCurry, Susan M, Mukherjee, Shubhabrata, Kowall, Neil W, McKee, Ann C, Honig, Robert A, Lawrence, S, Vonsattel, Jean Paul, Williamson, Jennifer, Small, Scott, Burke, James R, Hulette, Christine M, Welsh-Bohmer, Kathleen A, Gearing, Marla, Lah, James J, Levey, Allan I, Wingo, Thomas S, Apostolova, Liana G, Farlow, Martin R, Ghetti, Bernardino, Saykin, Andrew J, Spina, Salvatore, Albert, Marilyn S, Lyketsos, Constantine G, Troncoso, Juan C, Frosch, Matthew P, Green, Robert C, Growdon, John H, Hyman, Bradley T, Tanzi, Rudolph E, Potter, Huntington, Dickson, Dennis W, Ertekin-Taner, Nilufer, Graff-Radford, Neill R, Parisi, Joseph E, Petersen, Ronald C, Duara, Ranjan, Buxbaum, Joseph D, Goate, Alison M, Sano, Mary, Masurkar, Arjun V, Wisniewski, Thomas, Bigio, Eileen H, Mesulam, Marsel, Weintraub, Sandra, Vassar, Robert, Kaye, Jeffrey A, Quinn, Joseph F, Woltjer, Randall L, Barnes, Lisa L, Bennett, David A, Schneider, Julie A, Yu, Lei, Henderson, Victor, Fallon, Kenneth B, Harrell, Lindy E, Marson, Daniel C, Roberson, Erik D, DeCarli, Charles, Jin, Lee-Way, Olichney, John M, Kim, Ronald, LaFerla, Frank M, Monuki, Edwin, Head, Elizabeth, Sultzer, David, Geschwind, Daniel H, Vinters, Harry V, Chesselet, Marie-Francoise, Galasko, Douglas R, Brewer, James B, Boxer, Adam, Karydas, Anna, Kramer, Joel H, Miller, Bruce L, Rosen, Howard J, Seeley, William W, Burns, Jeffrey M, Swerdlow, Russell H, Abner, Erin, Van Eldik, Linda J, Albin, Roger L, Lieberman, Andrew P, Paulson, Henry L, Arnold, Steven E, Trojanowski, John Q, Van Deerlin, Vivianna M, Hamilton, Ronald L, Kamboh, M Ilyas, Lopez, Oscar L, and Becker, James T
Subjects: Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Aging, Prevention, Neurodegenerative, Acquired Cognitive Impairment, Alzheimer's Disease, Dementia, Minority Health, Health Disparities, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Genetics, 2.1 Biological and endogenous factors, Humans, Alleles, Polymorphism, Single Nucleotide, Alzheimer Disease, TDP-43 Proteinopathies, Progranulins, Membrane Proteins, Nerve Tissue Proteins, Sulfonylurea Receptors, Alzheimer’s Disease Genetics Consortium, KCNMB2, Diversity, Epidemiology, FTLD, Genome-Wide Association Studies, KATP, Neurology & Neurosurgery, Clinical sciences
Abstract: Limbic-predominant age-related TDP-43 encephalopathy (LATE) affects approximately one-third of older individuals and is associated with cognitive impairment. However, there is a highly incomplete understanding of the genetic determinants of LATE neuropathologic changes (LATE-NC) in diverse populations. The defining neuropathologic feature of LATE-NC is TDP-43 proteinopathy, often with comorbid hippocampal sclerosis (HS). In terms of genetic risk factors, LATE-NC and/or HS are associated with single nucleotide variants (SNVs) in 3 genes-TMEM106B (rs1990622), GRN (rs5848), and ABCC9 (rs1914361 and rs701478). We evaluated these 3 genes in convenience samples of individuals of African ancestry. The allele frequencies of the LATE-associated alleles were significantly different between persons of primarily African (versus European) ancestry: In persons of African ancestry, the risk-associated alleles for TMEM106B and ABCC9 were less frequent, whereas the risk allele in GRN was more frequent. We performed an exploratory analysis of data from African-American subjects processed by the Alzheimer's Disease Genomics Consortium, with a subset of African-American participants (n = 166) having corroborating neuropathologic data through the National Alzheimer's Coordinating Center (NACC). In this limited-size sample, the ABCC9/rs1914361 SNV was associated with HS pathology. More work is required concerning the genetic factors influencing non-Alzheimer disease pathology such as LATE-NC in diverse cohorts.
Published: 2023

2. Role of GBA variants in Lewy body disease neuropathology

Author: Walton, Ronald L., Koga, Shunsuke, Beasley, Alexandra I., White, Launia J., Griesacker, Teresa, Murray, Melissa E., Kasanuki, Koji, Hou, Xu, Fiesel, Fabienne C., Springer, Wolfdieter, Uitti, Ryan J., Fields, Julie A., Botha, Hugo, Ramanan, Vijay K., Kantarci, Kejal, Lowe, Val J., Jack, Clifford R., Ertekin-Taner, Nilufer, Savica, Rodolfo, Graff-Radford, Jonathan, Petersen, Ronald C., Parisi, Joseph E., Reichard, R. Ross, Graff-Radford, Neill R., Ferman, Tanis J., Boeve, Bradley F., Wszolek, Zbigniew K., Dickson, Dennis W., Ross, Owen A., and Heckman, Michael G.
Published: 2024
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3. Prioritization of Drug Targets for Neurodegenerative Diseases by Integrating Genetic and Proteomic Data From Brain and Blood

Author: Ferrari, Raffaele, Hernandez, Dena G., Nalls, Michael A., Rohrer, Jonathan D., Ramasamy, Adaikalavan, Kwok, John B.J., Dobson-Stone, Carol, Brooks, William S., Schofield, Peter R., Halliday, Glenda M., Hodges, John R., Piguet, Olivier, Bartley, Lauren, Thompson, Elizabeth, Haan, Eric, Hernández, Isabel, Ruiz, Agustín, Boada, Mercè, Borroni, Barbara, Padovani, Alessandro, Cruchaga, Carlos, Cairns, Nigel J., Benussi, Luisa, Binetti, Giuliano, Ghidoni, Roberta, Forloni, Gianluigi, Galimberti, Daniela, Fenoglio, Chiara, Serpente, Maria, Scarpini, Elio, Clarimón, Jordi, Lleó, Alberto, Blesa, Rafael, Waldö, Maria Landqvist, Nilsson, Karin, Nilsson, Christer, Mackenzie, Ian R.A., Hsiung, Ging-Yuek R., Mann, David M.A., Grafman, Jordan, Morris, Christopher M., Attems, Johannes, Griffiths, Timothy D., McKeith, Ian G., Thomas, Alan J., Pietrini, P., Huey, Edward D., Wassermann, Eric M., Baborie, Atik, Jaros, Evelyn, Tierney, Michael C., Pastor, Pau, Razquin, Cristina, Ortega-Cubero, Sara, Alonso, Elena, Perneczky, Robert, Diehl-Schmid, Janine, Alexopoulos, Panagiotis, Kurz, Alexander, Rainero, Innocenzo, Rubino, Elisa, Pinessi, Lorenzo, Rogaeva, Ekaterina, St. George-Hyslop, Peter, Rossi, Giacomina, Tagliavini, Fabrizio, Giaccone, Giorgio, Rowe, James B., Schlachetzki, Johannes C.M., Uphill, James, Collinge, John, Mead, Simon, Danek, Adrian, Van Deerlin, Vivianna M., Grossman, Murray, Trojanowski, John Q., van der Zee, Julie, Deschamps, William, Van Langenhove, Tim, Cruts, Marc, Van Broeckhoven, Christine, Cappa, Stefano F., Le Ber, Isabelle, Hannequin, Didier, Golfier, Véronique, Vercelletto, Martine, Brice, Alexis, Nacmias, Benedetta, Sorbi, Sandro, Bagnoli, Silvia, Piaceri, Irene, Nielsen, Jørgen E., Hjermind, Lena E., Riemenschneider, Matthias, Mayhaus, Manuel, Ibach, Bernd, Gasparoni, Gilles, Pichler, Sabrina, Gu, Wei, Rossor, Martin N., Fox, Nick C., Warren, Jason D., Spillantini, Maria Grazia, Morris, Huw R., Rizzu, Patrizia, Heutink, Peter, Snowden, Julie S., Rollinson, Sara, Richardson, Anna, Gerhard, Alexander, Bruni, Amalia C., Maletta, Raffaele, Frangipane, Francesca, Cupidi, Chiara, Bernardi, Livia, Anfossi, Maria, Gallo, Maura, Conidi, Maria Elena, Smirne, Nicoletta, Rademakers, Rosa, Baker, Matt, Dickson, Dennis W., Graff-Radford, Neill R., Petersen, Ronald C., Knopman, David, Josephs, Keith A., Boeve, Bradley F., Parisi, Joseph E., Seeley, William W., Miller, Bruce L., Karydas, Anna M., Rosen, Howard, van Swieten, John C., Dopper, Elise G.P., Seelaar, Harro, Pijnenburg, Yolande A.L., Scheltens, Philip, Logroscino, Giancarlo, Capozzo, Rosa, Novelli, Valeria, Puca, Annibale A., Franceschi, Massimo, Postiglione, Alfredo, Milan, Graziella, Sorrentino, Paolo, Kristiansen, Mark, Chiang, Huei-Hsin, Graff, Caroline, Pasquier, Florence, Rollin, Adeline, Deramecourt, Vincent, Lebert, Florence, Kapogiannis, Dimitrios, Ferrucci, Luigi, Pickering-Brown, Stuart, Singleton, Andrew B., Hardy, John, Momeni, Parastoo, Ge, Yi-Jun, Ou, Ya-Nan, Deng, Yue-Ting, Wu, Bang-Sheng, Yang, Liu, Zhang, Ya-Ru, Chen, Shi-Dong, Huang, Yu-Yuan, Dong, Qiang, Tan, Lan, and Yu, Jin-Tai
Published: 2023
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4. LATE to the PART-y

Author: Josephs, Keith A, Mackenzie, Ian, Frosch, Matthew P, Bigio, Eileen H, Neumann, Manuela, Arai, Tetsuaki, Dugger, Brittany N, Ghetti, Bernardino, Grossman, Murray, Hasegawa, Masato, Herrup, Karl, Holton, Janice, Jellinger, Kurt, Lashley, Tammaryn, McAleese, Kirsty E, Parisi, Joseph E, Revesz, Tamas, Saito, Yuko, Vonsattel, Jean Paul, Whitwell, Jennifer L, Wisniewski, Thomas, and Hu, William
Subjects: Biomedical and Clinical Sciences, Health Sciences, Psychology, Consensus, DNA-Binding Proteins, Humans, Limbic Encephalitis, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences
Published: 2019

5. Genome-wide analyses as part of the international FTLD-TDP whole-genome sequencing consortium reveals novel disease risk factors and increases support for immune dysfunction in FTLD

Author: Pottier, Cyril, Ren, Yingxue, Perkerson, Ralph B, Baker, Matt, Jenkins, Gregory D, van Blitterswijk, Marka, DeJesus-Hernandez, Mariely, van Rooij, Jeroen GJ, Murray, Melissa E, Christopher, Elizabeth, McDonnell, Shannon K, Fogarty, Zachary, Batzler, Anthony, Tian, Shulan, Vicente, Cristina T, Matchett, Billie, Karydas, Anna M, Hsiung, Ging-Yuek Robin, Seelaar, Harro, Mol, Merel O, Finger, Elizabeth C, Graff, Caroline, Öijerstedt, Linn, Neumann, Manuela, Heutink, Peter, Synofzik, Matthis, Wilke, Carlo, Prudlo, Johannes, Rizzu, Patrizia, Simon-Sanchez, Javier, Edbauer, Dieter, Roeber, Sigrun, Diehl-Schmid, Janine, Evers, Bret M, King, Andrew, Mesulam, M Marsel, Weintraub, Sandra, Geula, Changiz, Bieniek, Kevin F, Petrucelli, Leonard, Ahern, Geoffrey L, Reiman, Eric M, Woodruff, Bryan K, Caselli, Richard J, Huey, Edward D, Farlow, Martin R, Grafman, Jordan, Mead, Simon, Grinberg, Lea T, Spina, Salvatore, Grossman, Murray, Irwin, David J, Lee, Edward B, Suh, EunRan, Snowden, Julie, Mann, David, Ertekin-Taner, Nilufer, Uitti, Ryan J, Wszolek, Zbigniew K, Josephs, Keith A, Parisi, Joseph E, Knopman, David S, Petersen, Ronald C, Hodges, John R, Piguet, Olivier, Geier, Ethan G, Yokoyama, Jennifer S, Rissman, Robert A, Rogaeva, Ekaterina, Keith, Julia, Zinman, Lorne, Tartaglia, Maria Carmela, Cairns, Nigel J, Cruchaga, Carlos, Ghetti, Bernardino, Kofler, Julia, Lopez, Oscar L, Beach, Thomas G, Arzberger, Thomas, Herms, Jochen, Honig, Lawrence S, Vonsattel, Jean Paul, Halliday, Glenda M, Kwok, John B, White, Charles L, Gearing, Marla, Glass, Jonathan, Rollinson, Sara, Pickering-Brown, Stuart, Rohrer, Jonathan D, Trojanowski, John Q, Van Deerlin, Vivianna, Bigio, Eileen H, Troakes, Claire, Al-Sarraj, Safa, Asmann, Yan, Miller, Bruce L, Graff-Radford, Neill R, Boeve, Bradley F, and Seeley, William W
Subjects: Biomedical and Clinical Sciences, Neurosciences, Prevention, Brain Disorders, Biotechnology, Frontotemporal Dementia (FTD), Neurodegenerative, Human Genome, Aging, Dementia, Acquired Cognitive Impairment, Rare Diseases, Clinical Research, Alzheimer's Disease Related Dementias (ADRD), Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Genetics, 2.1 Biological and endogenous factors, Neurological, Aged, DNA Repeat Expansion, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Female, Frontal Lobe, Frontotemporal Lobar Degeneration, Genetic Predisposition to Disease, Genome-Wide Association Study, HLA-DQ Antigens, Humans, Intracellular Signaling Peptides and Proteins, Loss of Function Mutation, Male, Middle Aged, Nerve Tissue Proteins, Potassium Channels, Progranulins, Protein Serine-Threonine Kinases, Proteins, RNA, Messenger, Risk Factors, Sequence Analysis, RNA, Societies, Scientific, TDP-43 Proteinopathies, White People, Whole-genome sequencing FTLD-TDP, TBK1, DPP6, UNC13A, HLA, Immunity, Clinical Sciences, Neurology & Neurosurgery
Abstract: Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) represents the most common pathological subtype of FTLD. We established the international FTLD-TDP whole-genome sequencing consortium to thoroughly characterize the known genetic causes of FTLD-TDP and identify novel genetic risk factors. Through the study of 1131 unrelated Caucasian patients, we estimated that C9orf72 repeat expansions and GRN loss-of-function mutations account for 25.5% and 13.9% of FTLD-TDP patients, respectively. Mutations in TBK1 (1.5%) and other known FTLD genes (1.4%) were rare, and the disease in 57.7% of FTLD-TDP patients was unexplained by the known FTLD genes. To unravel the contribution of common genetic factors to the FTLD-TDP etiology in these patients, we conducted a two-stage association study comprising the analysis of whole-genome sequencing data from 517 FTLD-TDP patients and 838 controls, followed by targeted genotyping of the most associated genomic loci in 119 additional FTLD-TDP patients and 1653 controls. We identified three genome-wide significant FTLD-TDP risk loci: one new locus at chromosome 7q36 within the DPP6 gene led by rs118113626 (p value = 4.82e - 08, OR = 2.12), and two known loci: UNC13A, led by rs1297319 (p value = 1.27e - 08, OR = 1.50) and HLA-DQA2 led by rs17219281 (p value = 3.22e - 08, OR = 1.98). While HLA represents a locus previously implicated in clinical FTLD and related neurodegenerative disorders, the association signal in our study is independent from previously reported associations. Through inspection of our whole-genome sequence data for genes with an excess of rare loss-of-function variants in FTLD-TDP patients (n ≥ 3) as compared to controls (n = 0), we further discovered a possible role for genes functioning within the TBK1-related immune pathway (e.g., DHX58, TRIM21, IRF7) in the genetic etiology of FTLD-TDP. Together, our study based on the largest cohort of unrelated FTLD-TDP patients assembled to date provides a comprehensive view of the genetic landscape of FTLD-TDP, nominates novel FTLD-TDP risk loci, and strongly implicates the immune pathway in FTLD-TDP pathogenesis.
Published: 2019

6. Multisite study of the relationships between antemortem [11C]PIB‐PET Centiloid values and postmortem measures of Alzheimer's disease neuropathology

Author: La Joie, Renaud, Ayakta, Nagehan, Seeley, William W, Borys, Ewa, Boxer, Adam L, DeCarli, Charles, Doré, Vincent, Grinberg, Lea T, Huang, Eric, Hwang, Ji‐Hye, Ikonomovic, Milos D, Jack, Clifford, Jagust, William J, Jin, Lee‐Way, Klunk, William E, Kofler, Julia, Lesman‐Segev, Orit H, Lockhart, Samuel N, Lowe, Val J, Masters, Colin L, Mathis, Chester A, McLean, Catriona L, Miller, Bruce L, Mungas, Daniel, O'Neil, James P, Olichney, John M, Parisi, Joseph E, Petersen, Ronald C, Rosen, Howard J, Rowe, Christopher C, Spina, Salvatore, Vemuri, Prashanthi, Villemagne, Victor L, Murray, Melissa E, and Rabinovici, Gil D
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Alzheimer's Disease, Acquired Cognitive Impairment, Brain Disorders, Clinical Research, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Biomedical Imaging, Dementia, Aging, Neurosciences, Neurodegenerative, Aged, Alzheimer Disease, Aniline Compounds, Autopsy, Female, Humans, Male, Neuropathology, Plaque, Amyloid, Positron-Emission Tomography, Retrospective Studies, Thiazoles, beta-amyloid, Positron emission tomography, Centiloid, CERAD, Thal, Alzheimer's disease neuropathologic changes, Harmonization, Threshold, Pittsburgh compound-B, β-amyloid, Geriatrics, Clinical sciences, Biological psychology
Abstract: IntroductionWe sought to establish the relationships between standard postmortem measures of AD neuropathology and antemortem [11C]PIB-positron emission tomography ([11C]PIB-PET) analyzed with the Centiloid (CL) method, a standardized scale for Aβ-PET quantification.MethodsFour centers contributed 179 participants encompassing a broad range of clinical diagnoses, PET data, and autopsy findings.ResultsCL values increased with each CERAD neuritic plaque score increment (median -3 CL for no plaques and 92 CL for frequent plaques) and nonlinearly with Thal Aβ phases (increases were detected starting at phase 2) with overlap between scores/phases. PET-pathology associations were comparable across sites and unchanged when restricting the analyses to the 56 patients who died within 2 years of PET. A threshold of 12.2 CL detected CERAD moderate-to-frequent neuritic plaques (area under the curve = 0.910, sensitivity = 89.2%, specificity = 86.4%), whereas 24.4 CL identified intermediate-to-high AD neuropathological changes (area under the curve = 0.894, sensitivity = 84.1%, specificity = 87.9%).DiscussionOur study demonstrated the robustness of a multisite Centiloid [11C]PIB-PET study and established a range of pathology-based CL thresholds.
Published: 2019

7. A C6orf10/LOC101929163 locus is associated with age of onset in C9orf72 carriers.

Author: Zhang, Ming, Ferrari, Raffaele, Tartaglia, Maria Carmela, Keith, Julia, Surace, Ezequiel I, Wolf, Uri, Sato, Christine, Grinberg, Mark, Liang, Yan, Xi, Zhengrui, Dupont, Kyle, McGoldrick, Philip, Weichert, Anna, McKeever, Paul M, Schneider, Raphael, McCorkindale, Michael D, Manzoni, Claudia, Rademakers, Rosa, Graff-Radford, Neill R, Dickson, Dennis W, Parisi, Joseph E, Boeve, Bradley F, Petersen, Ronald C, Miller, Bruce L, Seeley, William W, van Swieten, John C, van Rooij, Jeroen, Pijnenburg, Yolande, van der Zee, Julie, Van Broeckhoven, Christine, Le Ber, Isabelle, Van Deerlin, Vivianna, Suh, EunRan, Rohrer, Jonathan D, Mead, Simon, Graff, Caroline, Öijerstedt, Linn, Pickering-Brown, Stuart, Rollinson, Sara, Rossi, Giacomina, Tagliavini, Fabrizio, Brooks, William S, Dobson-Stone, Carol, Halliday, Glenda M, Hodges, John R, Piguet, Olivier, Binetti, Giuliano, Benussi, Luisa, Ghidoni, Roberta, Nacmias, Benedetta, Sorbi, Sandro, Bruni, Amalia C, Galimberti, Daniela, Scarpini, Elio, Rainero, Innocenzo, Rubino, Elisa, Clarimon, Jordi, Lleó, Alberto, Ruiz, Agustin, Hernández, Isabel, Pastor, Pau, Diez-Fairen, Monica, Borroni, Barbara, Pasquier, Florence, Deramecourt, Vincent, Lebouvier, Thibaud, Perneczky, Robert, Diehl-Schmid, Janine, Grafman, Jordan, Huey, Edward D, Mayeux, Richard, Nalls, Michael A, Hernandez, Dena, Singleton, Andrew, Momeni, Parastoo, Zeng, Zhen, Hardy, John, Robertson, Janice, Zinman, Lorne, Rogaeva, Ekaterina, and International FTD-Genomics Consortium (IFGC)
Subjects: International FTD-Genomics Consortium, Humans, Amyotrophic Lateral Sclerosis, Age of Onset, DNA Methylation, Gene Expression Regulation, CpG Islands, Genotype, Heterozygote, Polymorphism, Single Nucleotide, Aged, Middle Aged, Female, Male, Frontotemporal Dementia, C9orf72 Protein, C9orf72, genetic association, age of onset, amyotrophic lateral sclerosis, frontotemporal dementia, Polymorphism, Single Nucleotide, Neurology & Neurosurgery, Medical and Health Sciences, Psychology and Cognitive Sciences
Abstract: The G4C2-repeat expansion in C9orf72 is the most common known cause of amyotrophic lateral sclerosis and frontotemporal dementia. The high phenotypic heterogeneity of C9orf72 patients includes a wide range in age of onset, modifiers of which are largely unknown. Age of onset could be influenced by environmental and genetic factors both of which may trigger DNA methylation changes at CpG sites. We tested the hypothesis that age of onset in C9orf72 patients is associated with some common single nucleotide polymorphisms causing a gain or loss of CpG sites and thus resulting in DNA methylation alterations. Combined analyses of epigenetic and genetic data have the advantage of detecting functional variants with reduced likelihood of false negative results due to excessive correction for multiple testing in genome-wide association studies. First, we estimated the association between age of onset in C9orf72 patients (n = 46) and the DNA methylation levels at all 7603 CpG sites available on the 450 k BeadChip that are mapped to common single nucleotide polymorphisms. This was followed by a genetic association study of the discovery (n = 144) and replication (n = 187) C9orf72 cohorts. We found that age of onset was reproducibly associated with polymorphisms within a 124.7 kb linkage disequilibrium block tagged by top-significant variation, rs9357140, and containing two overlapping genes (LOC101929163 and C6orf10). A meta-analysis of all 331 C9orf72 carriers revealed that every A-allele of rs9357140 reduced hazard by 30% (P = 0.0002); and the median age of onset in AA-carriers was 6 years later than GG-carriers. In addition, we investigated a cohort of C9orf72 negative patients (n = 2634) affected by frontotemporal dementia and/or amyotrophic lateral sclerosis; and also found that the AA-genotype of rs9357140 was associated with a later age of onset (adjusted P = 0.007 for recessive model). Phenotype analyses detected significant association only in the largest subgroup of patients with frontotemporal dementia (n = 2142, adjusted P = 0.01 for recessive model). Gene expression studies of frontal cortex tissues from 25 autopsy cases affected by amyotrophic lateral sclerosis revealed that the G-allele of rs9357140 is associated with increased brain expression of LOC101929163 (a non-coding RNA) and HLA-DRB1 (involved in initiating immune responses), while the A-allele is associated with their reduced expression. Our findings suggest that carriers of the rs9357140 GG-genotype (linked to an earlier age of onset) might be more prone to be in a pro-inflammatory state (e.g. by microglia) than AA-carriers. Further, investigating the functional links within the C6orf10/LOC101929163/HLA-DRB1 pathway will be critical to better define age-dependent pathogenesis of frontotemporal dementia and amyotrophic lateral sclerosis.
Published: 2018

8. Potential genetic modifiers of disease risk and age at onset in patients with frontotemporal lobar degeneration and GRN mutations: a genome-wide association study

Author: Pottier, Cyril, Zhou, Xiaolai, Perkerson, Ralph B, Baker, Matt, Jenkins, Gregory D, Serie, Daniel J, Ghidoni, Roberta, Benussi, Luisa, Binetti, Giuliano, de Munain, Adolfo López, Zulaica, Miren, Moreno, Fermin, Le Ber, Isabelle, Pasquier, Florence, Hannequin, Didier, Sánchez-Valle, Raquel, Antonell, Anna, Lladó, Albert, Parsons, Tammee M, Finch, NiCole A, Finger, Elizabeth C, Lippa, Carol F, Huey, Edward D, Neumann, Manuela, Heutink, Peter, Synofzik, Matthis, Wilke, Carlo, Rissman, Robert A, Slawek, Jaroslaw, Sitek, Emilia, Johannsen, Peter, Nielsen, Jørgen E, Ren, Yingxue, van Blitterswijk, Marka, DeJesus-Hernandez, Mariely, Christopher, Elizabeth, Murray, Melissa E, Bieniek, Kevin F, Evers, Bret M, Ferrari, Camilla, Rollinson, Sara, Richardson, Anna, Scarpini, Elio, Fumagalli, Giorgio G, Padovani, Alessandro, Hardy, John, Momeni, Parastoo, Ferrari, Raffaele, Frangipane, Francesca, Maletta, Raffaele, Anfossi, Maria, Gallo, Maura, Petrucelli, Leonard, Suh, EunRan, Lopez, Oscar L, Wong, Tsz H, van Rooij, Jeroen GJ, Seelaar, Harro, Mead, Simon, Caselli, Richard J, Reiman, Eric M, Sabbagh, Marwan Noel, Kjolby, Mads, Nykjaer, Anders, Karydas, Anna M, Boxer, Adam L, Grinberg, Lea T, Grafman, Jordan, Spina, Salvatore, Oblak, Adrian, Mesulam, M-Marsel, Weintraub, Sandra, Geula, Changiz, Hodges, John R, Piguet, Olivier, Brooks, William S, Irwin, David J, Trojanowski, John Q, Lee, Edward B, Josephs, Keith A, Parisi, Joseph E, Ertekin-Taner, Nilüfer, Knopman, David S, Nacmias, Benedetta, Piaceri, Irene, Bagnoli, Silvia, Sorbi, Sandro, Gearing, Marla, Glass, Jonathan, Beach, Thomas G, Black, Sandra E, Masellis, Mario, Rogaeva, Ekaterina, Vonsattel, Jean-Paul, Honig, Lawrence S, Kofler, Julia, Bruni, Amalia C, Snowden, Julie, Mann, David, and Pickering-Brown, Stuart
Subjects: Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Alzheimer's Disease Related Dementias (ADRD), Neurodegenerative, Clinical Research, Prevention, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Genetics, Rare Diseases, Human Genome, Dementia, Acquired Cognitive Impairment, Frontotemporal Dementia (FTD), Brain Disorders, 2.1 Biological and endogenous factors, Neurological, Age of Onset, Aged, Case-Control Studies, Cerebellum, Female, Frontotemporal Lobar Degeneration, Genetic Predisposition to Disease, Genome-Wide Association Study, Glial Cell Line-Derived Neurotrophic Factor Receptors, Humans, Male, Middle Aged, Mutation, Progranulins, RNA, Messenger, Neurology & Neurosurgery, Clinical sciences
Abstract: BackgroundLoss-of-function mutations in GRN cause frontotemporal lobar degeneration (FTLD). Patients with GRN mutations present with a uniform subtype of TAR DNA-binding protein 43 (TDP-43) pathology at autopsy (FTLD-TDP type A); however, age at onset and clinical presentation are variable, even within families. We aimed to identify potential genetic modifiers of disease onset and disease risk in GRN mutation carriers.MethodsThe study was done in three stages: a discovery stage, a replication stage, and a meta-analysis of the discovery and replication data. In the discovery stage, genome-wide logistic and linear regression analyses were done to test the association of genetic variants with disease risk (case or control status) and age at onset in patients with a GRN mutation and controls free of neurodegenerative disorders. Suggestive loci (p
Published: 2018

9. TDP-43-associated atrophy in brains with and without frontotemporal lobar degeneration

Author: Buciuc, Marina, Martin, Peter R., Tosakulwong, Nirubol, Murray, Melissa E., Petrucelli, Leonard, Senjem, Matthew L., Spychalla, Anthony J., Knopman, David S., Boeve, Bradley F., Petersen, Ronald C., Parisi, Joseph E., Reichard, R. Ross, Dickson, Dennis W., Jack, Clifford R., Jr., Whitwell, Jennifer L., and Josephs, Keith A.
Published: 2022
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10. Mitochondrial genomic variation in dementia with Lewy bodies: association with disease risk and neuropathological measures

Author: Valentino, Rebecca R., Ramnarine, Chloe, Heckman, Michael G., Johnson, Patrick W., Soto-Beasley, Alexandra I., Walton, Ronald L., Koga, Shunsuke, Kasanuki, Koji, Murray, Melissa E., Uitti, Ryan J., Fields, Julie A., Botha, Hugo, Ramanan, Vijay K., Kantarci, Kejal, Lowe, Val J., Jack, Clifford R., Ertekin-Taner, Nilufer, Savica, Rodolfo, Graff-Radford, Jonathan, Petersen, Ronald C., Parisi, Joseph E., Reichard, R. Ross, Graff-Radford, Neill R., Ferman, Tanis J., Boeve, Bradley F., Wszolek, Zbigniew K., Dickson, Dennis W., and Ross, Owen A.
Published: 2022
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11. Frontotemporal dementia with the V337M MAPT mutation

Author: Spina, Salvatore, Schonhaut, Daniel R, Boeve, Bradley F, Seeley, William W, Ossenkoppele, Rik, O'Neil, James P, Lazaris, Andreas, Rosen, Howard J, Boxer, Adam L, Perry, David C, Miller, Bruce L, Dickson, Dennis W, Parisi, Joseph E, Jagust, William J, Murray, Melissa E, and Rabinovici, Gil D
Subjects: Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Neurodegenerative, Alzheimer's Disease, Alzheimer's Disease Related Dementias (ADRD), Dementia, Acquired Cognitive Impairment, Frontotemporal Dementia (FTD), Biomedical Imaging, Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Rare Diseases, Aging, 2.1 Biological and endogenous factors, Neurological, Aged, Brain, Carbolines, Fatal Outcome, Female, Frontotemporal Dementia, Heterozygote, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Mutation, Positron-Emission Tomography, Radiopharmaceuticals, tau Proteins, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract: ObjectiveTo assess the efficacy of [18F]AV1451 PET in visualizing tau pathology in vivo in a patient with frontotemporal dementia (FTD) associated with the V337M microtubule-associated protein tau (MAPT) mutation.MethodsMAPT mutations are associated with the deposition of hyperphosphorylated tau protein in neurons and glia. The PET tracer [18F]AV1451 binds with high affinity to paired helical filaments tau that comprises neurofibrillary tangles in Alzheimer disease (AD), while postmortem studies suggest lower or absent binding to the tau filaments of the majority of non-AD tauopathies. We describe clinical, structural MRI, and [18F]AV1451 PET findings in a V337M MAPT mutation carrier affected by FTD and pathologic findings in his affected mother and in an unrelated V337M MAPT carrier also affected with FTD. The biochemical similarity between paired helical filament tau in AD and MAPT V337M predicts that the tau pathology associated with this mutation constitutes a compelling target for [18F]AV1451 imaging.ResultsWe found a strong association between topography and degree of [18F]AV1451 tracer retention in the proband and distribution of tau pathology in the brain of the proband's mother and the unrelated V337M mutation carrier. We also found a significant correlation between the degree of regional MRI brain atrophy and the extent of [18F]AV1451 binding in the proband and a strong association between the proband's clinical presentation and the extent of regional brain atrophy and tau accumulation as assessed by structural brain MRI and [18F]AV1451PET.ConclusionOur study supports the usefulness of [18F]AV1451 to characterize tau pathology in at least a subset of pathogenic MAPT mutations.
Published: 2017

12. Gene Expression Imputation Across Multiple Tissue Types Provides Insight Into the Genetic Architecture of Frontotemporal Dementia and Its Clinical Subtypes

Author: Ferrari, Raffaele, Hernandez, Dena G., Nalls, Michael A., Rohrer, Jonathan D., Ramasamy, Adaikalavan, Kwok, John B.J., Dobson-Stone, Carol, Brooks, William S., Schofield, Peter R., Halliday, Glenda M., Hodges, John R., Piguet, Olivier, Bartley, Lauren, Thompson, Elizabeth, Hernández, Isabel, Ruiz, Agustín, Boada, Mercè, Borroni, Barbara, Padovani, Alessandro, Cruchaga, Carlos, Cairns, Nigel J., Benussi, Luisa, Binetti, Giuliano, Ghidoni, Roberta, Forloni, Gianluigi, Galimberti, Daniela, Fenoglio, Chiara, Serpente, Maria, Scarpini, Elio, Clarimón, Jordi, Lleó, Alberto, Blesa, Rafael, Waldö, Maria Landqvist, Nilsson, Karin, Nilsson, Christer, Mackenzie, Ian R.A., Hsiung, Ging-Yuek R., Mann, David M.A., Grafman, Jordan, Morris, Christopher M., Attems, Johannes, Griffiths, Timothy D., McKeith, Ian G., Thomas, Alan J., Pietrini, Pietro, Huey, Edward D., Wassermann, Eric M., Baborie, Atik, Jaros, Evelyn, Tierney, Michael C., Pastor, Pau, Razquin, Cristina, Ortega-Cubero, Sara, Alonso, Elena, Perneczky, Robert, Diehl-Schmid, Janine, Alexopoulos, Panagiotis, Kurz, Alexander, Rainero, Innocenzo, Rubino, Elisa, Pinessi, Lorenzo, Rogaeva, Ekaterina, St. George-Hyslop, Peter, Rossi, Giacomina, Tagliavini, Fabrizio, Giaccone, Giorgio, Rowe, James B., Schlachetzki, Johannes C.M., Uphill, James, Collinge, John, Mead, Simon, Danek, Adrian, Van Deerlin, Vivianna M., Grossman, Murray, Trojanowski, John Q., van der Zee, Julie, Van Broeckhoven, Christine, Cappa, Stefano F., Le Ber, Isabelle, Hannequin, Didier, Golfier, Véronique, Vercelletto, Martine, Brice, Alexis, Nacmias, Benedetta, Sorbi, Sandro, Bagnoli, Silvia, Piaceri, Irene, Nielsen, Jørgen E., Hjermind, Lena E., Riemenschneider, Matthias, Mayhaus, Manuel, Ibach, Bernd, Gasparoni, Gilles, Pichler, Sabrina, Gu, Wei, Rossor, Martin N., Fox, Nick C., Warren, Jason D., Spillantini, Maria Grazia, Morris, Huw R., Rizzu, Patrizia, Heutink, Peter, Snowden, Julie S., Rollinson, Sara, Richardson, Anna, Gerhard, Alexander, Bruni, Amalia C., Maletta, Raffaele, Frangipane, Francesca, Cupidi, Chiara, Bernardi, Livia, Anfossi, Maria, Gallo, Maura, Conidi, Maria Elena, Smirne, Nicoletta, Rademakers, Rosa, Baker, Matt, Dickson, Dennis W., Graff-Radford, Neill R., Petersen, Ronald C., Knopman, David, Josephs, Keith A., Boeve, Bradley F., Parisi, Joseph E., Seeley, William W., Miller, Bruce L., Karydas, Anna M., Rosen, Howard, van Swieten, John C., Dopper, Elise G.P., Seelaar, Harro, Pijnenburg, Yolande A.L., Scheltens, Philip, Logroscino, Giancarlo, Capozzo, Rosa, Novelli, Valeria, Puca, Annibale A., Franceschi, Massimo, Postiglione, Alfredo, Milan, Graziella, Sorrentino, Paolo, Kristiansen, Mark, Chiang, Huei-Hsin, Graff, Caroline, Pasquier, Florence, Rollin, Adeline, Deramecourt, Vincent, Lebert, Florence, Kapogiannis, Dimitrios, Ferrucci, Luigi, Pickering-Brown, Stuart, Singleton, Andrew B., Hardy, John, Momeni, Parastoo, Reus, Lianne M., Pasaniuc, Bogdan, Posthuma, Danielle, Boltz, Toni, and Ophoff, Roel A.
Published: 2021
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13. Association between transactive response DNA-binding protein of 43 kDa type and cognitive resilience to Alzheimer’s disease: a case-control study

Author: Buciuc, Marina, Whitwell, Jennifer L., Tosakulwong, Nirubol, Weigand, Stephen D., Murray, Melissa E., Boeve, Bradley F., Knopman, David S., Parisi, Joseph E., Petersen, Ronald C., Dickson, Dennis W., and Josephs, Keith A.
Published: 2020
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14. Altered brain energetics induces mitochondrial fission arrest in Alzheimer's Disease.

Author: Zhang, Liang, Trushin, Sergey, Christensen, Trace A, Bachmeier, Benjamin V, Gateno, Benjamin, Schroeder, Andreas, Yao, Jia, Itoh, Kie, Sesaki, Hiromi, Poon, Wayne W, Gylys, Karen H, Patterson, Emily R, Parisi, Joseph E, Diaz Brinton, Roberta, Salisbury, Jeffrey L, and Trushina, Eugenia
Subjects: Brain, Mitochondria, Animals, Mice, Transgenic, Mice, Knockout, Alzheimer Disease, Disease Models, Animal, Dynamins, Amyloid beta-Protein Precursor, Energy Metabolism, Phosphorylation, Phenotype, CA1 Region, Hippocampal, Mitochondrial Dynamics, Hypoxia, Mice, Transgenic, Knockout, Disease Models, Animal, CA1 Region, Hippocampal
Abstract: Altered brain metabolism is associated with progression of Alzheimer's Disease (AD). Mitochondria respond to bioenergetic changes by continuous fission and fusion. To account for three dimensional architecture of the brain tissue and organelles, we applied 3-dimensional electron microscopy (3D EM) reconstruction to visualize mitochondrial structure in the brain tissue from patients and mouse models of AD. We identified a previously unknown mitochondrial fission arrest phenotype that results in elongated interconnected organelles, "mitochondria-on-a-string" (MOAS). Our data suggest that MOAS formation may occur at the final stages of fission process and was not associated with altered translocation of activated dynamin related protein 1 (Drp1) to mitochondria but with reduced GTPase activity. Since MOAS formation was also observed in the brain tissue of wild-type mice in response to hypoxia or during chronological aging, fission arrest may represent fundamental compensatory adaptation to bioenergetic stress providing protection against mitophagy that may preserve residual mitochondrial function. The discovery of novel mitochondrial phenotype that occurs in the brain tissue in response to energetic stress accurately detected only using 3D EM reconstruction argues for a major role of mitochondrial dynamics in regulating neuronal survival.
Published: 2016

15. A large-scale comparison of cortical thickness and volume methods for measuring Alzheimer's disease severity

Author: Schwarz, Christopher G, Gunter, Jeffrey L, Wiste, Heather J, Przybelski, Scott A, Weigand, Stephen D, Ward, Chadwick P, Senjem, Matthew L, Vemuri, Prashanthi, Murray, Melissa E, Dickson, Dennis W, Parisi, Joseph E, Kantarci, Kejal, Weiner, Michael W, Petersen, Ronald C, Jack, Clifford R, and Initiative, Alzheimer's Disease Neuroimaging
Subjects: Biomedical and Clinical Sciences, Biological Psychology, Clinical and Health Psychology, Neurosciences, Psychology, Neurodegenerative, Brain Disorders, Alzheimer's Disease, Acquired Cognitive Impairment, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Clinical Research, Neurological, Adult, Aged, Aged, 80 and over, Alzheimer Disease, Brain Mapping, Cerebral Cortex, Cognitive Dysfunction, Cohort Studies, Datasets as Topic, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Psychiatric Status Rating Scales, Alzheimer's Disease Neuroimaging Initiative, Biological psychology, Clinical and health psychology
Abstract: Alzheimer's disease (AD) researchers commonly use MRI as a quantitative measure of disease severity. Historically, hippocampal volume has been favored. Recently, "AD signature" measurements of gray matter (GM) volumes or cortical thicknesses have gained attention. Here, we systematically evaluate multiple thickness- and volume-based candidate-methods side-by-side, built using the popular FreeSurfer, SPM, and ANTs packages, according to the following criteria: (a) ability to separate clinically normal individuals from those with AD; (b) (extent of) correlation with head size, a nuisance covariatel (c) reliability on repeated scans; and (d) correlation with Braak neurofibrillary tangle stage in a group with autopsy. We show that volume- and thickness-based measures generally perform similarly for separating clinically normal from AD populations, and in correlation with Braak neurofibrillary tangle stage at autopsy. Volume-based measures are generally more reliable than thickness measures. As expected, volume measures are highly correlated with head size, while thickness measures are generally not. Because approaches to statistically correcting volumes for head size vary and may be inadequate to deal with this underlying confound, and because our goal is to determine a measure which can be used to examine age and sex effects in a cohort across a large age range, we thus recommend thickness-based measures. Ultimately, based on these criteria and additional practical considerations of run-time and failure rates, we recommend an AD signature measure formed from a composite of thickness measurements in the entorhinal, fusiform, parahippocampal, mid-temporal, inferior-temporal, and angular gyrus ROIs using ANTs with input segmentations from SPM12.
Published: 2016

16. TDP-43 is associated with a reduced likelihood of rendering a clinical diagnosis of dementia with Lewy bodies in autopsy-confirmed cases of transitional/diffuse Lewy body disease

Author: Buciuc, Marina, Whitwell, Jennifer L., Boeve, Bradley F., Ferman, Tanis J., Graff-Radford, Jonathan, Savica, Rodolfo, Kantarci, Kejal, Fields, Julie A., Knopman, David S., Petersen, Ronald C., Parisi, Joseph E., Murray, Melissa E., Dickson, Dennis W., and Josephs, Keith A.
Published: 2020
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17. Developmental Disorders

Author: Kotagal, Suresh, Bicknese, Alma R., Eswara, Marthand, Fenton, Glen A., Geller, Thomas J., Grange, Dorothy K., Nigro, Michael A., Parisi, Joseph E., Pittman, Thomas, Wong-Kisiel, Lily, and Rosenberg, Roger N., editor
Published: 2019
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18. Novel clinical associations with specific C9ORF72 transcripts in patients with repeat expansions in C9ORF72

Author: van Blitterswijk, Marka, Gendron, Tania F, Baker, Matthew C, DeJesus-Hernandez, Mariely, Finch, NiCole A, Brown, Patricia H, Daughrity, Lillian M, Murray, Melissa E, Heckman, Michael G, Jiang, Jie, Lagier-Tourenne, Clotilde, Edbauer, Dieter, Cleveland, Don W, Josephs, Keith A, Parisi, Joseph E, Knopman, David S, Petersen, Ronald C, Petrucelli, Leonard, Boeve, Bradley F, Graff-Radford, Neill R, Boylan, Kevin B, Dickson, Dennis W, and Rademakers, Rosa
Subjects: Biomedical and Clinical Sciences, Neurosciences, Brain Disorders, Acquired Cognitive Impairment, Dementia, Genetics, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, C9orf72 Protein, Cerebellum, DNA Repeat Expansion, Female, Frontal Lobe, Frontotemporal Dementia, Genetic Association Studies, Genetic Variation, Heterozygote, Humans, Introns, Male, Middle Aged, Motor Neuron Disease, Promoter Regions, Genetic, Proteins, Survival Analysis, Tissue Banks, C9ORF72, Frontotemporal dementia, Frontotemporal lobar degeneration, Motor neuron disease, Amyotrophic lateral sclerosis, Disease modifier, Clinical Sciences, Neurology & Neurosurgery
Abstract: The loss of chromosome 9 open reading frame 72 (C9ORF72) expression, associated with C9ORF72 repeat expansions, has not been examined systematically. Three C9ORF72 transcript variants have been described thus far; the GGGGCC repeat is located between two non-coding exons (exon 1a and exon 1b) in the promoter region of transcript variant 2 (NM_018325.4) or in the first intron of variant 1 (NM_145005.6) and variant 3 (NM_001256054.2). We studied C9ORF72 expression in expansion carriers (n = 56) for whom cerebellum and/or frontal cortex was available. Using quantitative real-time PCR and digital molecular barcoding techniques, we assessed total C9ORF72 transcripts, variant 1, variant 2, variant 3, and intron containing transcripts [upstream of the expansion (intron 1a) and downstream of the expansion (intron 1b)]; the latter were correlated with levels of poly(GP) and poly(GA) proteins aberrantly translated from the expansion as measured by immunoassay (n = 50). We detected a decrease in expansion carriers as compared to controls for total C9ORF72 transcripts, variant 1, and variant 2: the strongest association was observed for variant 2 (quantitative real-time PCR cerebellum: median 43 %, p = 1.26e-06, and frontal cortex: median 58 %, p = 1.11e-05; digital molecular barcoding cerebellum: median 31 %, p = 5.23e-10, and frontal cortex: median 53 %, p = 5.07e-10). Importantly, we revealed that variant 1 levels greater than the 25th percentile conferred a survival advantage [digital molecular barcoding cerebellum: hazard ratio (HR) 0.31, p = 0.003, and frontal cortex: HR 0.23, p = 0.0001]. When focusing on intron containing transcripts, analysis of the frontal cortex revealed an increase of potentially truncated transcripts in expansion carriers as compared to controls [digital molecular barcoding frontal cortex (intron 1a): median 272 %, p = 0.003], with the highest levels in patients pathologically diagnosed with frontotemporal lobar degeneration. In the cerebellum, our analysis suggested that transcripts were less likely to be truncated and, excitingly, we discovered that intron containing transcripts were associated with poly(GP) levels [digital molecular barcoding cerebellum (intron 1a): r = 0.33, p = 0.02, and (intron 1b): r = 0.49, p = 0.0004] and poly(GA) levels [digital molecular barcoding cerebellum (intron 1a): r = 0.34, p = 0.02, and (intron 1b): r = 0.38, p = 0.007]. In summary, we report decreased expression of specific C9ORF72 transcripts and provide support for the presence of truncated transcripts as well as pre-mRNAs that may serve as templates for RAN translation. We further show that higher C9ORF72 levels may have beneficial effects, which warrants caution in the development of new therapeutic approaches.
Published: 2015

19. Distinct pathological phenotypes of Creutzfeldt-Jakob disease in recipients of prion-contaminated growth hormone

Author: Cali, Ignazio, Miller, Cathleen J, Parisi, Joseph E, Geschwind, Michael D, Gambetti, Pierluigi, and Schonberger, Lawrence B
Subjects: Paediatrics, Biomedical and Clinical Sciences, Brain Disorders, Transmissible Spongiform Encephalopathy (TSE), Infectious Diseases, Neurodegenerative, Emerging Infectious Diseases, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Neurological, Adult, Aged, Aged, 80 and over, Autopsy, Brain, Creutzfeldt-Jakob Syndrome, Encephalopathy, Bovine Spongiform, Female, Growth Hormone, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neurologic Examination, Phenotype, PrPSc Proteins, Severity of Illness Index, Iatrogenic Creutzfeldt-Jakob disease, PrPSc, Growth hormone, Dura mater, Pathological phenotype, Biochemistry and Cell Biology, Clinical Sciences, Neurosciences, Biochemistry and cell biology
Abstract: IntroductionThe present study compares the clinical, pathological and molecular features of a United States (US) case of growth hormone (GH)-associated Creutzfeldt-Jakob disease (GH-CJD) (index case) to those of two earlier referred US cases of GH-CJD and one case of dura mater (d)-associated CJD (dCJD). All iatrogenic CJD (iCJD) subjects were methionine (M) homozygous at codon 129 (129MM) of the prion protein (PrP) gene and had scrapie prion protein (PrP(Sc)) type 1 (iCJDMM1).ResultsThe index subject presented with ataxia, weight loss and changes in the sleep pattern about 38 years after the midpoint of GH treatment. Autopsy examination revealed a neuropathological phenotype reminiscent of both sCJDMV2-K (a sporadic CJD subtype in subjects methionine/valine heterozygous at codon 129 with PrP(Sc) type 2 and the presence of kuru plaques) and variant CJD (vCJD). The two earlier cases of GH-CJDMM1 and the one of dCJDMM1 were associated with neuropathological phenotypes that differed from that of the index case mainly because they lacked PrP plaques. The phenotype of the earlier GH-CJDMM1 cases shared several, but not all, characteristics with sCJDMM1, whereas dCJDMM1 was phenotypically indistinguishable from sCJDMM1. Two distinct groups of dCJDMM1 have also been described in Japan based on clinical features, the presence or absence of PrP plaques and distinct PK-resistant PrP(Sc) (resPrP(Sc)) electrophoretic mobilities. The resPrP(Sc) electrophoretic mobility was, however, identical in our GH-CJDMM1 and dCJDMM1 cases, and matched that of sCJDMM1.ConclusionsOur study shows that receipt of prion-contaminated GH can lead to a prion disease with molecular features (129MM and PrP(Sc) type 2) and phenotypic characteristics that differ from those of sporadic prion disease (sCJDMM1), a difference that may reflect adaptation of "heterologous" prion strains to the 129MM background.
Published: 2015

20. Cerebellar c9RAN proteins associate with clinical and neuropathological characteristics of C9ORF72 repeat expansion carriers

Author: Gendron, Tania F, van Blitterswijk, Marka, Bieniek, Kevin F, Daughrity, Lillian M, Jiang, Jie, Rush, Beth K, Pedraza, Otto, Lucas, John A, Murray, Melissa E, Desaro, Pamela, Robertson, Amelia, Overstreet, Karen, Thomas, Colleen S, Crook, Julia E, Castanedes-Casey, Monica, Rousseau, Linda, Josephs, Keith A, Parisi, Joseph E, Knopman, David S, Petersen, Ronald C, Boeve, Bradley F, Graff-Radford, Neill R, Rademakers, Rosa, Lagier-Tourenne, Clotilde, Edbauer, Dieter, Cleveland, Don W, Dickson, Dennis W, Petrucelli, Leonard, and Boylan, Kevin B
Subjects: Genetics, Frontotemporal Dementia (FTD), Alzheimer's Disease Related Dementias (ADRD), Brain Disorders, Neurodegenerative, Rare Diseases, Clinical Research, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, ALS, Neurosciences, Acquired Cognitive Impairment, 2.1 Biological and endogenous factors, Aetiology, Neurological, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, C9orf72 Protein, Cerebellum, Cognition Disorders, Cohort Studies, DNA Repeat Expansion, Female, Frontal Lobe, Frontotemporal Dementia, Heterozygote, Hippocampus, Humans, Male, Middle Aged, Motor Cortex, Motor Neuron Disease, Protein Biosynthesis, Proteins, RNA, Messenger, Amyotrophic lateral sclerosis, C9ORF72 repeat expansion, c9RAN proteins, Cognition, Dipeptide repeat proteins, Frontotemporal dementia, Frontotemporal lobar degeneration, Neuropathological diagnosis, Repeat-associated non-ATG translation, Clinical Sciences, Neurology & Neurosurgery
Abstract: Clinical and neuropathological characteristics associated with G4C2 repeat expansions in chromosome 9 open reading frame 72 (C9ORF72), the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, are highly variable. To gain insight on the molecular basis for the heterogeneity among C9ORF72 mutation carriers, we evaluated associations between features of disease and levels of two abundantly expressed "c9RAN proteins" produced by repeat-associated non-ATG (RAN) translation of the expanded repeat. For these studies, we took a departure from traditional immunohistochemical approaches and instead employed immunoassays to quantitatively measure poly(GP) and poly(GA) levels in cerebellum, frontal cortex, motor cortex, and/or hippocampus from 55 C9ORF72 mutation carriers [12 patients with ALS, 24 with frontotemporal lobar degeneration (FTLD) and 19 with FTLD with motor neuron disease (FTLD-MND)]. We additionally investigated associations between levels of poly(GP) or poly(GA) and cognitive impairment in 15 C9ORF72 ALS patients for whom neuropsychological data were available. Among the neuroanatomical regions investigated, poly(GP) levels were highest in the cerebellum. In this same region, associations between poly(GP) and both neuropathological and clinical features were detected. Specifically, cerebellar poly(GP) levels were significantly lower in patients with ALS compared to patients with FTLD or FTLD-MND. Furthermore, cerebellar poly(GP) associated with cognitive score in our cohort of 15 patients. In the cerebellum, poly(GA) levels similarly trended lower in the ALS subgroup compared to FTLD or FTLD-MND subgroups, but no association between cerebellar poly(GA) and cognitive score was detected. Both cerebellar poly(GP) and poly(GA) associated with C9ORF72 variant 3 mRNA expression, but not variant 1 expression, repeat size, disease onset, or survival after onset. Overall, these data indicate that cerebellar abnormalities, as evidenced by poly(GP) accumulation, associate with neuropathological and clinical phenotypes, in particular cognitive impairment, of C9ORF72 mutation carriers.
Published: 2015

21. Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy.

Author: Kouri, Naomi, Ross, Owen A, Dombroski, Beth, Younkin, Curtis S, Serie, Daniel J, Soto-Ortolaza, Alexandra, Baker, Matthew, Finch, Ni Cole A, Yoon, Hyejin, Kim, Jungsu, Fujioka, Shinsuke, McLean, Catriona A, Ghetti, Bernardino, Spina, Salvatore, Cantwell, Laura B, Farlow, Martin R, Grafman, Jordan, Huey, Edward D, Ryung Han, Mi, Beecher, Sherry, Geller, Evan T, Kretzschmar, Hans A, Roeber, Sigrun, Gearing, Marla, Juncos, Jorge L, Vonsattel, Jean Paul G, Van Deerlin, Vivianna M, Grossman, Murray, Hurtig, Howard I, Gross, Rachel G, Arnold, Steven E, Trojanowski, John Q, Lee, Virginia M, Wenning, Gregor K, White, Charles L, Höglinger, Günter U, Müller, Ulrich, Devlin, Bernie, Golbe, Lawrence I, Crook, Julia, Parisi, Joseph E, Boeve, Bradley F, Josephs, Keith A, Wszolek, Zbigniew K, Uitti, Ryan J, Graff-Radford, Neill R, Litvan, Irene, Younkin, Steven G, Wang, Li-San, Ertekin-Taner, Nilüfer, Rademakers, Rosa, Hakonarsen, Hakon, Schellenberg, Gerard D, and Dickson, Dennis W
Subjects: Cerebral Cortex, Humans, Basal Ganglia Diseases, Supranuclear Palsy, Progressive, Neurodegenerative Diseases, Kinesin, SOS1 Protein, tau Proteins, Myelin Proteins, Case-Control Studies, Polymorphism, Single Nucleotide, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Genome-Wide Association Study, Young Adult, RNA, Long Noncoding, and over, Polymorphism, Single Nucleotide, RNA, Long Noncoding, Supranuclear Palsy, Progressive
Abstract: Corticobasal degeneration (CBD) is a neurodegenerative disorder affecting movement and cognition, definitively diagnosed only at autopsy. Here, we conduct a genome-wide association study (GWAS) in CBD cases (n=152) and 3,311 controls, and 67 CBD cases and 439 controls in a replication stage. Associations with meta-analysis were 17q21 at MAPT (P=1.42 × 10(-12)), 8p12 at lnc-KIF13B-1, a long non-coding RNA (rs643472; P=3.41 × 10(-8)), and 2p22 at SOS1 (rs963731; P=1.76 × 10(-7)). Testing for association of CBD with top progressive supranuclear palsy (PSP) GWAS single-nucleotide polymorphisms (SNPs) identified associations at MOBP (3p22; rs1768208; P=2.07 × 10(-7)) and MAPT H1c (17q21; rs242557; P=7.91 × 10(-6)). We previously reported SNP/transcript level associations with rs8070723/MAPT, rs242557/MAPT, and rs1768208/MOBP and herein identified association with rs963731/SOS1. We identify new CBD susceptibility loci and show that CBD and PSP share a genetic risk factor other than MAPT at 3p22 MOBP (myelin-associated oligodendrocyte basic protein).
Published: 2015

22. Neuroimaging correlates with neuropathologic schemes in neurodegenerative disease

Author: Lowe, Val J., Lundt, Emily S., Albertson, Sabrina M., Przybelski, Scott A., Senjem, Matthew L., Parisi, Joseph E., Kantarci, Kejal, Boeve, Bradley, Jones, David T., Knopman, David, Jack, Clifford R., Jr., Dickson, Dennis W., Petersen, Ronald C., and Murray, Melissa E.
Published: 2019
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23. The influence of tau, amyloid, alpha-synuclein, TDP-43, and vascular pathology in clinically normal elderly individuals

Author: Wennberg, Alexandra M., Whitwell, Jennifer L., Tosakulwong, Nirubol, Weigand, Stephen D., Murray, Melissa E., Machulda, Mary M., Petrucelli, Leonard, Mielke, Michelle M., Jack, Clifford R., Jr., Knopman, David S., Parisi, Joseph E., Petersen, Ronald C., Dickson, Dennis W., and Josephs, Keith A.
Published: 2019
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24. Ataxin-2 as potential disease modifier in C9ORF72 expansion carriers

Author: van Blitterswijk, Marka, Mullen, Bianca, Heckman, Michael G, Baker, Matthew C, DeJesus-Hernandez, Mariely, Brown, Patricia H, Murray, Melissa E, Hsiung, Ging-Yuek R, Stewart, Heather, Karydas, Anna M, Finger, Elizabeth, Kertesz, Andrew, Bigio, Eileen H, Weintraub, Sandra, Mesulam, Marsel, Hatanpaa, Kimmo J, White, Charles L, Neumann, Manuela, Strong, Michael J, Beach, Thomas G, Wszolek, Zbigniew K, Lippa, Carol, Caselli, Richard, Petrucelli, Leonard, Josephs, Keith A, Parisi, Joseph E, Knopman, David S, Petersen, Ronald C, Mackenzie, Ian R, Seeley, William W, Grinberg, Lea T, Miller, Bruce L, Boylan, Kevin B, Graff-Radford, Neill R, Boeve, Bradley F, Dickson, Dennis W, and Rademakers, Rosa
Subjects: Biomedical and Clinical Sciences, Neurosciences, Acquired Cognitive Impairment, Rare Diseases, Brain Disorders, Genetics, ALS, Dementia, Neurodegenerative, Frontotemporal Dementia (FTD), Aging, Alzheimer's Disease Related Dementias (ADRD), Clinical Research, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), 2.1 Biological and endogenous factors, Neurological, Adult, Ataxins, C9orf72 Protein, Cohort Studies, DNA Repeat Expansion, Frontotemporal Dementia, Genetic Association Studies, Heterozygote, Humans, Male, Membrane Proteins, Middle Aged, Motor Neuron Disease, Nerve Tissue Proteins, Proteins, Survival of Motor Neuron 1 Protein, Survival of Motor Neuron 2 Protein, C9ORF72, Ataxin-2, ATXN2, Motor neuron disease, Amyotrophic lateral sclerosis, Frontotemporal dementia, Disease modifier, Clinical Sciences, Neurology & Neurosurgery, Biological psychology
Abstract: Repeat expansions in chromosome 9 open reading frame 72 (C9ORF72) are an important cause of both motor neuron disease (MND) and frontotemporal dementia (FTD). Currently, little is known about factors that could account for the phenotypic heterogeneity detected in C9ORF72 expansion carriers. In this study, we investigated 4 genes that could represent genetic modifiers: ataxin-2 (ATXN2), non-imprinted in Prader-Willi/Angelman syndrome 1 (NIPA1), survival motor neuron 1 (SMN1), and survival motor neuron 2 (SMN2). Assessment of these genes, in a unique cohort of 331 C9ORF72 expansion carriers and 376 control subjects, revealed that intermediate repeat lengths in ATXN2 possibly act as disease modifier in C9ORF72 expansion carriers; no evidence was provided for a potential role of NIPA1, SMN1, or SMN2. The effects of intermediate ATXN2 repeats were most profound in probands with MND or FTD/MND (2.1% vs. 0% in control subjects, p = 0.013), whereas the frequency in probands with FTD was identical to control subjects. Though intermediate ATXN2 repeats were already known to be associated with MND risk, previous reports did not focus on individuals with clear pathogenic mutations, such as repeat expansions in C9ORF72. Based on our present findings, we postulate that intermediate ATXN2 repeat lengths may render C9ORF72 expansion carriers more susceptible to the development of MND; further studies are needed, however, to validate our findings.
Published: 2014

25. TMEM106B protects C9ORF72 expansion carriers against frontotemporal dementia

Author: van Blitterswijk, Marka, Mullen, Bianca, Nicholson, Alexandra M, Bieniek, Kevin F, Heckman, Michael G, Baker, Matthew C, DeJesus-Hernandez, Mariely, Finch, NiCole A, Brown, Patricia H, Murray, Melissa E, Hsiung, Ging-Yuek R, Stewart, Heather, Karydas, Anna M, Finger, Elizabeth, Kertesz, Andrew, Bigio, Eileen H, Weintraub, Sandra, Mesulam, Marsel, Hatanpaa, Kimmo J, White III, Charles L, Strong, Michael J, Beach, Thomas G, Wszolek, Zbigniew K, Lippa, Carol, Caselli, Richard, Petrucelli, Leonard, Josephs, Keith A, Parisi, Joseph E, Knopman, David S, Petersen, Ronald C, Mackenzie, Ian R, Seeley, William W, Grinberg, Lea T, Miller, Bruce L, Boylan, Kevin B, Graff-Radford, Neill R, Boeve, Bradley F, Dickson, Dennis W, and Rademakers, Rosa
Subjects: Biomedical and Clinical Sciences, Neurosciences, Dementia, Frontotemporal Dementia (FTD), Neurodegenerative, Alzheimer's Disease Related Dementias (ADRD), Genetics, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), ALS, Human Genome, Clinical Research, Rare Diseases, Acquired Cognitive Impairment, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Neurological, Adult, Age of Onset, Aged, Aged, 80 and over, Alleles, C9orf72 Protein, Cohort Studies, DNA Repeat Expansion, DNA-Binding Proteins, Female, Frontotemporal Dementia, Genetic Predisposition to Disease, Genotype, Heterozygote, Humans, Male, Membrane Proteins, Middle Aged, Models, Genetic, Motor Neuron Disease, Nerve Tissue Proteins, Polymorphism, Single Nucleotide, Proteins, C9ORF72, TMEM106B, Frontotemporal dementia, Motor neuron disease, Amyotrophic lateral sclerosis, Disease modifier, Clinical Sciences, Neurology & Neurosurgery
Abstract: Variants in transmembrane protein 106 B (TMEM106B) modify the disease penetrance of frontotemporal dementia (FTD) in carriers of progranulin (GRN) mutations. We investigated whether TMEM106B is also a genetic modifier of disease in carriers of chromosome 9 open reading frame 72 (C9ORF72) expansions. We assessed the genotype of 325 C9ORF72 expansion carriers (cohort 1), 586 FTD patients lacking C9ORF72 expansions [with or without motor neuron disease (MND); cohort 2], and a total of 1,302 controls for TMEM106B variants (rs3173615 and rs1990622) using MassArray iPLEX and Taqman genotyping assays. For our primary analysis, we focused on functional variant rs3173615, and employed a recessive genotypic model. In cohort 1, patients with C9ORF72 expansions showed a significantly reduced frequency of carriers homozygous for the minor allele as compared to controls [11.9 vs. 19.1 %, odds ratio (OR) 0.57, p = 0.014; same direction as carriers of GRN mutations]. The strongest evidence was provided by FTD patients (OR 0.33, p = 0.009) followed by FTD/MND patients (OR 0.38, p = 0.017), whereas no significant difference was observed in MND patients (OR 0.85, p = 0.55). In cohort 2, the frequency of carriers homozygous for the minor allele was not significantly reduced in patients as compared to controls (OR 0.77, p = 0.079); however, a significant reduction was observed when focusing on those patients with frontotemporal lobar degeneration and TAR DNA-binding protein 43 inclusions (FTLD-TDP; OR 0.26, p < 0.001). Our study identifies TMEM106B as the first genetic factor modifying disease presentation in C9ORF72 expansion carriers. Homozygosity for the minor allele protects carriers from developing FTD, but not from developing MND; similar effects are seen in FTLD-TDP patients with yet unknown genetic causes. These new findings show that the protective effects of TMEM106B are not confined to carriers of GRN mutations and might be relevant for prognostic testing, and as a promising therapeutic target for the entire spectrum of FTLD-TDP.
Published: 2014

26. Distinct cytokine profiles in human brains resilient to Alzheimer's pathology

Author: Barroeta-Espar, Isabel, Weinstock, Laura D., Perez-Nievas, Beatriz G., Meltzer, Avery C., Siao Tick Chong, Michael, Amaral, Ana C., Murray, Melissa E., Moulder, Krista L., Morris, John C., Cairns, Nigel J., Parisi, Joseph E., Lowe, Val J., Petersen, Ronald C., Kofler, Julia, Ikonomovic, Milos D., López, Oscar, Klunk, William E., Mayeux, Richard P., Frosch, Matthew P., Wood, Levi B., and Gomez-Isla, Teresa
Published: 2019
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27. MRI and pathology of REM sleep behavior disorder in dementia with Lewy bodies

Author: Murray, Melissa E, Ferman, Tanis J, Boeve, Bradley F, Przybelski, Scott A, Lesnick, Timothy G, Liesinger, Amanda M, Senjem, Matthew L, Gunter, Jeffrey L, Preboske, Gregory M, Lowe, Val J, Vemuri, Prashanthi, Dugger, Brittany N, Knopman, David S, Smith, Glenn E, Parisi, Joseph E, Silber, Michael H, Graff-Radford, Neill R, Petersen, Ronald C, Jack, Clifford R, Dickson, Dennis W, and Kantarci, Kejal
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Alzheimer's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aging, Dementia, Lewy Body Dementia, Acquired Cognitive Impairment, Neurodegenerative, Neurosciences, Sleep Research, Brain Disorders, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Neurological, Aged, Aged, 80 and over, Amyloid beta-Peptides, Autopsy, Brain, Cohort Studies, Female, Humans, Image Processing, Computer-Assisted, Lewy Body Disease, Likelihood Functions, Magnetic Resonance Imaging, Male, REM Sleep Behavior Disorder, Retrospective Studies, Severity of Illness Index, alpha-Synuclein, tau Proteins, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract: ObjectiveTo determine structural MRI and digital microscopic characteristics of REM sleep behavior disorder in individuals with low-, intermediate-, and high-likelihood dementia with Lewy bodies (DLB) at autopsy.MethodsPatients with autopsy-confirmed low-, intermediate-, and high-likelihood DLB, according to the probability statement recommended by the third report of the DLB Consortium, and antemortem MRI, were identified (n = 75). The clinical history was assessed for presence (n = 35) and absence (n = 40) of probable REM sleep behavior disorder (pRBD), and patients' antemortem MRIs were compared using voxel-based morphometry. Pathologic burdens of phospho-tau, β-amyloid, and α-synuclein were measured in regions associated with early neuropathologic involvement, the hippocampus and amygdala.ResultspRBD was present in 21 patients (60%) with high-likelihood, 12 patients (34%) with intermediate-likelihood, and 2 patients (6%) with low-likelihood DLB. Patients with pRBD were younger, more likely to be male (p ≤ 0.001), and had a more frequent neuropathologic diagnosis of diffuse (neocortical) Lewy body disease. In the hippocampus and amygdala, phospho-tau and β-amyloid burden were lower in patients with pRBD compared with those without pRBD (p < 0.01). α-Synuclein burden did not differ in the hippocampus, but trended in the amygdala. Patients without pRBD had greater atrophy of temporoparietal cortices, hippocampus, and amygdala (p < 0.001) than those with pRBD; atrophy of the hippocampus (p = 0.005) and amygdala (p = 0.02) were associated with greater phospho-tau burdens in these regions.ConclusionPresence of pRBD is associated with a higher likelihood of DLB and less severe Alzheimer-related pathology in the medial temporal lobes, whereas absence of pRBD is characterized by Alzheimer-like atrophy patterns on MRI and increased phospho-tau burden.
Published: 2013

28. Pathological, imaging and genetic characteristics support the existence of distinct TDP-43 types in non-FTLD brains

Author: Josephs, Keith A., Murray, Melissa E., Tosakulwong, Nirubol, Weigand, Stephen D., Serie, Amanda M., Perkerson, Ralph B., Matchett, Billie J., Jack, Jr., Clifford R., Knopman, David S., Petersen, Ronald C., Parisi, Joseph E., Petrucelli, Leonard, Baker, Matthew, Rademakers, Rosa, Whitwell, Jennifer L., and Dickson, Dennis W.
Published: 2019
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29. FUS pathology defines the majority of tau- and TDP-43-negative frontotemporal lobar degeneration.

Author: Urwin, Hazel, Josephs, Keith A, Rohrer, Jonathan D, Mackenzie, Ian R, Neumann, Manuela, Authier, Astrid, Seelaar, Harro, Van Swieten, John C, Brown, Jeremy M, Johannsen, Peter, Nielsen, Jorgen E, Holm, Ida E, FReJA Consortium, Dickson, Dennis W, Rademakers, Rosa, Graff-Radford, Neill R, Parisi, Joseph E, Petersen, Ronald C, Hatanpaa, Kimmo J, White, Charles L, Weiner, Myron F, Geser, Felix, Van Deerlin, Vivianna M, Trojanowski, John Q, Miller, Bruce L, Seeley, William W, van der Zee, Julie, Kumar-Singh, Samir, Engelborghs, Sebastiaan, De Deyn, Peter P, Van Broeckhoven, Christine, Bigio, Eileen H, Deng, Han-Xiang, Halliday, Glenda M, Kril, Jillian J, Munoz, David G, Mann, David M, Pickering-Brown, Stuart M, Doodeman, Valerie, Adamson, Gary, Ghazi-Noori, Shabnam, Fisher, Elizabeth MC, Holton, Janice L, Revesz, Tamas, Rossor, Martin N, Collinge, John, Mead, Simon, and Isaacs, Adrian M
Subjects: FReJA Consortium, Hippocampus, Frontal Lobe, Humans, Dyskinesias, RNA-Binding Protein FUS, tau Proteins, DNA-Binding Proteins, Prevalence, Sequence Analysis, DNA, Mental Disorders, Age of Onset, Mutation, Adult, Middle Aged, Female, Male, Frontotemporal Lobar Degeneration, Sequence Analysis, DNA, Clinical Sciences, Neurosciences, Neurology & Neurosurgery
Abstract: Through an international consortium, we have collected 37 tau- and TAR DNA-binding protein 43 (TDP-43)-negative frontotemporal lobar degeneration (FTLD) cases, and present here the first comprehensive analysis of these cases in terms of neuropathology, genetics, demographics and clinical data. 92% (34/37) had fused in sarcoma (FUS) protein pathology, indicating that FTLD-FUS is an important FTLD subtype. This FTLD-FUS collection specifically focussed on aFTLD-U cases, one of three recently defined subtypes of FTLD-FUS. The aFTLD-U subtype of FTLD-FUS is characterised clinically by behavioural variant frontotemporal dementia (bvFTD) and has a particularly young age of onset with a mean of 41 years. Further, this subtype had a high prevalence of psychotic symptoms (36% of cases) and low prevalence of motor symptoms (3% of cases). We did not find FUS mutations in any aFTLD-U case. To date, the only subtype of cases reported to have ubiquitin-positive but tau-, TDP-43- and FUS-negative pathology, termed FTLD-UPS, is the result of charged multivesicular body protein 2B gene (CHMP2B) mutation. We identified three FTLD-UPS cases, which are negative for CHMP2B mutation, suggesting that the full complement of FTLD pathologies is yet to be elucidated.
Published: 2010

30. Rates of hippocampal atrophy and presence of post-mortem TDP-43 in patients with Alzheimer's disease: a longitudinal retrospective study

Author: Josephs, Keith A, Dickson, Dennis W, Tosakulwong, Nirubol, Weigand, Stephen D, Murray, Melissa E, Petrucelli, Leonard, Liesinger, Amanda M, Senjem, Matthew L, Spychalla, Anthony J, Knopman, David S, Parisi, Joseph E, Petersen, Ronald C, Jack, Clifford R, Jr, and Whitwell, Jennifer L
Published: 2017
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31. Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia

Author: Rademakers, Rosa, Eriksen, Jason L, Baker, Matt, Robinson, Todd, Ahmed, Zeshan, Lincoln, Sarah J, Finch, Nicole, Rutherford, Nicola J, Crook, Richard J, Josephs, Keith A, Boeve, Bradley F, Knopman, David S, Petersen, Ronald C, Parisi, Joseph E, Caselli, Richard J, Wszolek, Zbigniew K, Uitti, Ryan J, Feldman, Howard, Hutton, Michael L, Mackenzie, Ian R, Graff-Radford, Neill R, and Dickson, Dennis W
Subjects: Rare Diseases, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurosciences, Brain Disorders, Neurodegenerative, Frontotemporal Dementia (FTD), Dementia, Acquired Cognitive Impairment, Genetics, Alzheimer's Disease Related Dementias (ADRD), Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Neurological, Aged, Base Sequence, Binding Sites, Brain, DNA-Binding Proteins, Female, Gene Expression Regulation, Genetic Variation, Genotype, Humans, Intercellular Signaling Peptides and Proteins, Male, MicroRNAs, Middle Aged, Molecular Sequence Data, Mutation, Progranulins, Protein Biosynthesis, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract: Loss-of-function mutations in progranulin (GRN) cause ubiquitin- and TAR DNA-binding protein 43 (TDP-43)-positive frontotemporal dementia (FTLD-U), a progressive neurodegenerative disease affecting approximately 10% of early-onset dementia patients. Here we expand the role of GRN in FTLD-U and demonstrate that a common genetic variant (rs5848), located in the 3'-untranslated region (UTR) of GRN in a binding-site for miR-659, is a major susceptibility factor for FTLD-U. In a series of pathologically confirmed FTLD-U patients without GRN mutations, we show that carriers homozygous for the T-allele of rs5848 have a 3.2-fold increased risk to develop FTLD-U compared with homozygous C-allele carriers (95% CI: 1.50-6.73). We further demonstrate that miR-659 can regulate GRN expression in vitro, with miR-659 binding more efficiently to the high risk T-allele of rs5848 resulting in augmented translational inhibition of GRN. A significant reduction in GRN protein was observed in homozygous T-allele carriers in vivo, through biochemical and immunohistochemical methods, mimicking the effect of heterozygous loss-of-function GRN mutations. In support of these findings, the neuropathology of homozygous rs5848 T-allele carriers frequently resembled the pathological FTLD-U subtype of GRN mutation carriers. We suggest that the expression of GRN is regulated by miRNAs and that common genetic variability in a miRNA binding-site can significantly increase the risk for FTLD-U. Translational regulation by miRNAs may represent a common mechanism underlying complex neurodegenerative disorders.
Published: 2008

32. White-matter integrity on DTI and the pathologic staging of Alzheimer's disease

Author: Kantarci, Kejal, Murray, Melissa E., Schwarz, Christopher G., Reid, Robert I., Przybelski, Scott A., Lesnick, Timothy, Zuk, Samantha M., Raman, Mekala R., Senjem, Matthew L., Gunter, Jeffrey L., Boeve, Bradley F., Knopman, David S., Parisi, Joseph E., Petersen, Ronald C., Jack, Clifford R., Jr., and Dickson, Dennis W.
Published: 2017
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33. Transethnic genome-wide scan identifies novel Alzheimer's disease loci

Author: Adams, Perrie M., Albert, Marilyn S., Albin, Roger L., Apostolova, Liana G., Arnold, Steven E., Asthana, Sanjay, Atwood, Craig S., Barmada, Michjael M., Barnes, Lisa L., Beach, Thomas G., Becker, James T., Bigio, Eileen H., Bird, Thomas D., Blacker, Deborah, Boeve, Bradley F., Bowen, James D., Boxer, Adam, Burke, James R., Cairns, Nigel J., Cao, Chuanhai, Carlson, Chris S., Carlsson, Cynthia M., Carney, Regina M., Carrasquillo, Minerva M., Carroll, Steven L., Chui, Helena C., Clark, David G., Corneveaux, Jason, Cribbs, David H., Crocco, Elizabeth A., Cruchaga, Carlos, De Jager, Philip L., DeCarli, Charles, DeKosky, Steven T., Demirci, F. Yesim, Dick, Malcolm, Dickson, Dennis W., Doody, Rachelle S., Duara, Ranjan, Ertekin-Taner, Nilufer, Faber, Kelley M., Fairchild, Thomas J., Fallon, Kenneth B., Farlow, Martin R., Ferris, Steven, Frosch, Matthew P., Galasko, Douglas R., Gearing, Marla, Geschwind, Daniel H., Ghetti, Bernardino, Gilbert, John R., Glass, Jonathan D., Graff-Radford, Neill R., Green, Robert C., Growdon, John H., Hakonarson, Hakon, Hamilton, Ronald L., Hardy, John, Harrell, Lindy E., Head, Elizabeth, Honig, Lawrence S., Huebinger, Ryan M., Huentelman, Matthew J., Hulette, Christine M., Hyman, Bradley T., Jarvik, Gail P., Jicha, Gregory A., Jin, Lee-Way, Karydas, Anna, Kauwe, John S.K., Kaye, Jeffrey A., Kim, Ronald, Koo, Edward H., Kowall, Neil W., Kramer, Joel H., LaFerla, Frank M., Lah, James J., Leverenz, James B., Levey, Allan I., Li, Ge, Lieberman, Andrew P., Lin, Chiao-Feng, Lopez, Oscar L., Lyketsos, Constantine G., Mack, Wendy J., Marson, Daniel C., Martiniuk, Frank, Mash, Deborah C., Masliah, Eliezer, McCormick, Wayne C., McCurry, Susan M., McDavid, Andrew N., McKee, Ann C., Mesulam, Marsel, Miller, Bruce L., Miller, Carol A., Miller, Joshua W., Morris, John C., Mukherjee, Shubhabrata, Murrell, Jill R., Myers, Amanda J., O'Bryant, Sid, Olichney, John M., Pankratz, Vernon S., Parisi, Joseph E., Partch, Amanda, Paulson, Henry L., Perry, William, Peskind, Elaine, Petersen, Ronald C., Pierce, Aimee, Poon, Wayne W., Potter, Huntington, Quinn, Joseph F., Raj, Ashok, Raskind, Murray, Reisberg, Barry, Reisch, Joan S., Reitz, Christiane, Ringman, John M., Roberson, Erik D., Rogaeva, Ekaterina, Rosen, Howard J., Rosenberg, Roger N., Royall, Donald R., Sager, Mark A., Sano, Mary, Saykin, Andrew J., Schneider, Julie A., Schneider, Lon S., Seeley, William W., Smith, Amanda G., Sonnen, Joshua A., Spina, Salvatore, Stern, Robert A., Tanzi, Rudolph E., Thornton-Wells, Tricia A., Trojanowski, John Q., Troncoso, Juan C., Tsuang, Debby W., Van Deerlin, Vivianna M., Van Eldik, Linda J., Vardarajan, Badri N., Vinters, Harry V., Vonsattel, Jean Paul, Weintraub, Sandra, Welsh-Bohmer, Kathleen A., Williamson, Jennifer, Wishnek, Sarah, Woltjer, Randall L., Wright, Clinton B., Wu, Chuang-Kuo, Yu, Chang-En, Yu, Lei, Zhang, Xiaoling, Jun, Gyungah R., Chung, Jaeyoon, Mez, Jesse, Barber, Robert, Beecham, Gary W., Bennett, David A., Buxbaum, Joseph D., Byrd, Goldie S., Crane, Paul K., De Jager, Philip, Evans, Denis, Fallin, M. Danielle, Foroud, Tatiana M., Friedland, Robert P., Goate, Alison M., Hendrie, Hugh, Hall, Kathleen S., Hamilton-Nelson, Kara L., Inzelberg, Rivka, Kamboh, M. Ilyas, Kukull, Walter A., Kunkle, Brian W., Kuwano, Ryozo, Larson, Eric B., Logue, Mark W., Manly, Jennifer J., Martin, Eden R., Montine, Thomas J., Naj, Adam, Reiman, Eric M., Sherva, Richard, St. George-Hyslop, Peter H., Thornton, Timothy, Younkin, Steven G., Wang, Li-San, Wendlund, Jens R., Winslow, Ashley R., Haines, Jonathan, Mayeux, Richard, Pericak-Vance, Margaret A., Schellenberg, Gerard, Lunetta, Kathryn L., and Farrer, Lindsay A.
Published: 2017
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34. An investigation of cerebrovascular lesions in dementia with Lewy bodies compared to Alzheimer's disease

Author: Sarro, Lidia, Tosakulwong, Nirubol, Schwarz, Christopher G., Graff-Radford, Jonathan, Przybelski, Scott A., Lesnick, Timothy G., Zuk, Samantha M., Reid, Robert I., Raman, Mekala R., Boeve, Bradley F., Ferman, Tanis J., Knopman, David S., Comi, Giancarlo, Filippi, Massimo, Murray, Melissa E., Parisi, Joseph E., Dickson, Dennis W., Petersen, Ronald C., Jack, Clifford R., Jr., and Kantarci, Kejal
Published: 2017
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35. Longitudinal anatomic, functional, and molecular characterization of Pick disease phenotypes

Author: Whitwell, Jennifer L., Tosakulwong, Nirubol, Schwarz, Christopher C., Senjem, Matthew L., Spychalla, Anthony J., Duffy, Joseph R., Graff-Radford, Jon, Machulda, Mary M., Boeve, Bradley F., Knopman, David S., Petersen, Ronald C., Lowe, Val J., Jack, Clifford R., Jr, Dickson, Dennis W., Parisi, Joseph E., and Josephs, Keith A.
Published: 2020
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36. Subtypes of dementia with Lewy bodies are associated with α-synuclein and tau distribution

Author: Ferman, Tanis J., Aoki, Naoya, Boeve, Bradley F., Aakre, Jeremiah A., Kantarci, Kejal, Graff-Radford, Jonathan, Parisi, Joseph E., Van Gerpen, Jay A., Graff-Radford, Neill R., Uitti, Ryan J., Pedraza, Otto, Murray, Melissa E., Wszolek, Zbigniew K., Reichard, R. Ross, Fields, Julie A., Ross, Owen A., Knopman, David S., Petersen, Ronald C., and Dickson, Dennis W.
Published: 2020
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37. Utility of FDG-PET in diagnosis of Alzheimer-related TDP-43 proteinopathy

Author: Buciuc, Marina, Botha, Hugo, Murray, Melissa E., Schwarz, Christopher G., Senjem, Matthew L., Jones, David T., Knopman, David S., Boeve, Bradley F., Petersen, Ronald C., Jack, Clifford R., Jr, Petrucelli, Leonard, Parisi, Joseph E., Dickson, Dennis W., Lowe, Val, Whitwell, Jennifer L., and Josephs, Keith A.
Published: 2020
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38. Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifiesLRRC4C, LHX5-AS1and nominates ancestry-specific lociPTPRK,GRB14, andKIAA0825as novel risk loci for Alzheimer’s disease: the Alzheimer’s Disease Genetics Consortium

Author: Rajabli, Farid, primary, Benchek, Penelope, additional, Tosto, Giuseppe, additional, Kushch, Nicholas, additional, Sha, Jin, additional, Bazemore, Katrina, additional, Zhu, Congcong, additional, Lee, Wan-Ping, additional, Haut, Jacob, additional, Hamilton-Nelson, Kara L., additional, Wheeler, Nicholas R., additional, Zhao, Yi, additional, Farrell, John J., additional, Grunin, Michelle A., additional, Leung, Yuk Yee, additional, Kuksa, Pavel P., additional, Li, Donghe, additional, Lucio da Fonseca, Eder, additional, Mez, Jesse B., additional, Palmer, Ellen L., additional, Pillai, Jagan, additional, Sherva, Richard M., additional, Song, Yeunjoo E., additional, Zhang, Xiaoling, additional, Iqbal, Taha, additional, Pathak, Omkar, additional, Valladares, Otto, additional, Kuzma, Amanda B., additional, Abner, Erin, additional, Adams, Perrie M., additional, Aguirre, Alyssa, additional, Albert, Marilyn S., additional, Albin, Roger L., additional, Allen, Mariet, additional, Alvarez, Lisa, additional, Apostolova, Liana G., additional, Arnold, Steven E., additional, Asthana, Sanjay, additional, Atwood, Craig S., additional, Ayres, Gayle, additional, Baldwin, Clinton T., additional, Barber, Robert C., additional, Barnes, Lisa L., additional, Barral, Sandra, additional, Beach, Thomas G., additional, Becker, James T., additional, Beecham, Gary W., additional, Beekly, Duane, additional, Benitez, Bruno A., additional, Bennett, David, additional, Bertelson, John, additional, Bird, Thomas D., additional, Blacker, Deborah, additional, Boeve, Bradley F., additional, Bowen, James D., additional, Boxer, Adam, additional, Brewer, James, additional, Burke, James R., additional, Burns, Jeffrey M., additional, Buxbaum, Joseph D., additional, Cairns, Nigel J., additional, Cantwell, Laura B., additional, Cao, Chuanhai, additional, Carlson, Christopher S., additional, Carlsson, Cynthia M., additional, Carney, Regina M., additional, Carrasquillo, Minerva M., additional, Chasse, Scott, additional, Chesselet, Marie-Francoise, additional, Chin, Nathaniel A., additional, Chui, Helena C., additional, Chung, Jaeyoon, additional, Craft, Suzanne, additional, Crane, Paul K., additional, Cribbs, David H., additional, Crocco, Elizabeth A., additional, Cruchaga, Carlos, additional, Cuccaro, Michael L., additional, Cullum, Munro, additional, Darby, Eveleen, additional, Davis, Barbara, additional, De Jager, Philip L., additional, DeCarli, Charles, additional, DeToledo, John, additional, Dick, Malcolm, additional, Dickson, Dennis W., additional, Dombroski, Beth A., additional, Doody, Rachelle S., additional, Duara, Ranjan, additional, Ertekin-Taner, NIlüfer, additional, Evans, Denis A., additional, Faber, Kelley M., additional, Fairchild, Thomas J., additional, Fallon, Kenneth B., additional, Fardo, David W., additional, Farlow, Martin R., additional, Fernandez-Hernandez, Victoria, additional, Ferris, Steven, additional, Foroud, Tatiana M., additional, Frosch, Matthew P., additional, Fulton-Howard, Brian, additional, Galasko, Douglas R., additional, Gamboa, Adriana, additional, Gearing, Marla, additional, Geschwind, Daniel H., additional, Ghetti, Bernardino, additional, Gilbert, John R., additional, Goate, Alison M., additional, Grabowski, Thomas J., additional, Graff-Radford, Neill R., additional, Green, Robert C., additional, Growdon, John H., additional, Hakonarson, Hakon, additional, Hall, James, additional, Hamilton, Ronald L., additional, Harari, Oscar, additional, Hardy, John, additional, Harrell, Lindy E., additional, Head, Elizabeth, additional, Henderson, Victor W., additional, Hernandez, Michelle, additional, Hohman, Timothy, additional, Honig, Lawrence S., additional, Huebinger, Ryan M., additional, Huentelman, Matthew J., additional, Hulette, Christine M., additional, Hyman, Bradley T., additional, Hynan, Linda S., additional, Ibanez, Laura, additional, Jarvik, Gail P., additional, Jayadev, Suman, additional, Jin, Lee-Way, additional, Johnson, Kim, additional, Johnson, Leigh, additional, Kamboh, M. Ilyas, additional, Karydas, Anna M., additional, Katz, Mindy J., additional, Kauwe, John S., additional, Kaye, Jeffrey A., additional, Keene, C. Dirk, additional, Khaleeq, Aisha, additional, Kim, Ronald, additional, Knebl, Janice, additional, Kowall, Neil W., additional, Kramer, Joel H., additional, Kukull, Walter A., additional, LaFerla, Frank M., additional, Lah, James J., additional, Larson, Eric B., additional, Lerner, Alan, additional, Leverenz, James B., additional, Levey, Allan I., additional, Lieberman, Andrew P., additional, Lipton, Richard B., additional, Logue, Mark, additional, Lopez, Oscar L., additional, Lunetta, Kathryn L., additional, Lyketsos, Constantine G., additional, Mains, Douglas, additional, Margaret, Flanagan E., additional, Marson, Daniel C., additional, Martin, Eden R R., additional, Martiniuk, Frank, additional, Mash, Deborah C., additional, Masliah, Eliezer, additional, Massman, Paul, additional, Masurkar, Arjun, additional, McCormick, Wayne C., additional, McCurry, Susan M., additional, McDavid, Andrew N., additional, McDonough, Stefan, additional, McKee, Ann C., additional, Mesulam, Marsel, additional, Miller, Bruce L., additional, Miller, Carol A., additional, Miller, Joshua W., additional, Montine, Thomas J., additional, Monuki, Edwin S., additional, Morris, John C., additional, Mukherjee, Shubhabrata, additional, Myers, Amanda J., additional, Nguyen, Trung, additional, O’Bryant, Sid, additional, Olichney, John M., additional, Ory, Marcia, additional, Palmer, Raymond, additional, Parisi, Joseph E., additional, Paulson, Henry L., additional, Pavlik, Valory, additional, Paydarfar, David, additional, Perez, Victoria, additional, Peskind, Elaine, additional, Petersen, Ronald C., additional, Pierce, Aimee, additional, Polk, Marsha, additional, Poon, Wayne W., additional, Potter, Huntington, additional, Qu, Liming, additional, Quiceno, Mary, additional, Quinn, Joseph F., additional, Raj, Ashok, additional, Raskind, Murray, additional, Reiman, Eric M., additional, Reisberg, Barry, additional, Reisch, Joan S., additional, Ringman, John M., additional, Roberson, Erik D., additional, Rodriguear, Monica, additional, Rogaeva, Ekaterina, additional, Rosen, Howard J., additional, Rosenberg, Roger N., additional, Royall, Donald R., additional, Sager, Mark A., additional, Sano, Mary, additional, Saykin, Andrew J., additional, Schneider, Julie A., additional, Schneider, Lon S., additional, Seeley, William W., additional, Slifer, Susan H., additional, Small, Scott, additional, Smith, Amanda G., additional, Smith, Janet P., additional, Sonnen, Joshua A., additional, Spina, Salvatore, additional, St George-Hyslop, Peter, additional, Stern, Robert A., additional, Stevens, Alan B., additional, Strittmatter, Stephen M., additional, Sultzer, David, additional, Swerdlow, Russell H., additional, Tanzi, Rudolph E., additional, Tilson, Jeffrey L., additional, Trojanowski, John Q., additional, Troncoso, Juan C., additional, Tsuang, Debby W., additional, Van Deerlin, Vivianna M., additional, van Eldik, Linda J., additional, Vance, Jeffery M., additional, Vardarajan, Badri N., additional, Vassar, Robert, additional, Vinters, Harry V., additional, Vonsattel, Jean-Paul, additional, Weintraub, Sandra, additional, Welsh-Bohmer, Kathleen A., additional, Whitehead, Patrice L., additional, Wijsman, Ellen M., additional, Wilhelmsen, Kirk C., additional, Williams, Benjamin, additional, Williamson, Jennifer, additional, Wilms, Henrik, additional, Wingo, Thomas S., additional, Wisniewski, Thomas, additional, Woltjer, Randall L., additional, Woon, Martin, additional, Wright, Clinton B., additional, Wu, Chuang-Kuo, additional, Younkin, Steven G., additional, Yu, Chang-En, additional, Yu, Lei, additional, Zhu, Xiongwei, additional, Kunkle, Brian W., additional, Bush, William S., additional, Wang, Li-San, additional, Farrer, Lindsay A., additional, Haines, Jonathan L., additional, Mayeux, Richard, additional, Pericak-Vance, Margaret A., additional, Schellenberg, Gerard D., additional, Jun, Gyungah R., additional, Reitz, Christiane, additional, and Naj, Adam C., additional
Published: 2023
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39. Prioritization of Drug Targets for Neurodegenerative Diseases by Integrating Genetic and Proteomic Data From Brain and Blood

Author: Ge, Yi-Jun, primary, Ou, Ya-Nan, additional, Deng, Yue-Ting, additional, Wu, Bang-Sheng, additional, Yang, Liu, additional, Zhang, Ya-Ru, additional, Chen, Shi-Dong, additional, Huang, Yu-Yuan, additional, Dong, Qiang, additional, Tan, Lan, additional, Yu, Jin-Tai, additional, Ferrari, Raffaele, additional, Hernandez, Dena G., additional, Nalls, Michael A., additional, Rohrer, Jonathan D., additional, Ramasamy, Adaikalavan, additional, Kwok, John B.J., additional, Dobson-Stone, Carol, additional, Brooks, William S., additional, Schofield, Peter R., additional, Halliday, Glenda M., additional, Hodges, John R., additional, Piguet, Olivier, additional, Bartley, Lauren, additional, Thompson, Elizabeth, additional, Haan, Eric, additional, Hernández, Isabel, additional, Ruiz, Agustín, additional, Boada, Mercè, additional, Borroni, Barbara, additional, Padovani, Alessandro, additional, Cruchaga, Carlos, additional, Cairns, Nigel J., additional, Benussi, Luisa, additional, Binetti, Giuliano, additional, Ghidoni, Roberta, additional, Forloni, Gianluigi, additional, Galimberti, Daniela, additional, Fenoglio, Chiara, additional, Serpente, Maria, additional, Scarpini, Elio, additional, Clarimón, Jordi, additional, Lleó, Alberto, additional, Blesa, Rafael, additional, Waldö, Maria Landqvist, additional, Nilsson, Karin, additional, Nilsson, Christer, additional, Mackenzie, Ian R.A., additional, Hsiung, Ging-Yuek R., additional, Mann, David M.A., additional, Grafman, Jordan, additional, Morris, Christopher M., additional, Attems, Johannes, additional, Griffiths, Timothy D., additional, McKeith, Ian G., additional, Thomas, Alan J., additional, Pietrini, P., additional, Huey, Edward D., additional, Wassermann, Eric M., additional, Baborie, Atik, additional, Jaros, Evelyn, additional, Tierney, Michael C., additional, Pastor, Pau, additional, Razquin, Cristina, additional, Ortega-Cubero, Sara, additional, Alonso, Elena, additional, Perneczky, Robert, additional, Diehl-Schmid, Janine, additional, Alexopoulos, Panagiotis, additional, Kurz, Alexander, additional, Rainero, Innocenzo, additional, Rubino, Elisa, additional, Pinessi, Lorenzo, additional, Rogaeva, Ekaterina, additional, St. George-Hyslop, Peter, additional, Rossi, Giacomina, additional, Tagliavini, Fabrizio, additional, Giaccone, Giorgio, additional, Rowe, James B., additional, Schlachetzki, Johannes C.M., additional, Uphill, James, additional, Collinge, John, additional, Mead, Simon, additional, Danek, Adrian, additional, Van Deerlin, Vivianna M., additional, Grossman, Murray, additional, Trojanowski, John Q., additional, van der Zee, Julie, additional, Deschamps, William, additional, Van Langenhove, Tim, additional, Cruts, Marc, additional, Van Broeckhoven, Christine, additional, Cappa, Stefano F., additional, Le Ber, Isabelle, additional, Hannequin, Didier, additional, Golfier, Véronique, additional, Vercelletto, Martine, additional, Brice, Alexis, additional, Nacmias, Benedetta, additional, Sorbi, Sandro, additional, Bagnoli, Silvia, additional, Piaceri, Irene, additional, Nielsen, Jørgen E., additional, Hjermind, Lena E., additional, Riemenschneider, Matthias, additional, Mayhaus, Manuel, additional, Ibach, Bernd, additional, Gasparoni, Gilles, additional, Pichler, Sabrina, additional, Gu, Wei, additional, Rossor, Martin N., additional, Fox, Nick C., additional, Warren, Jason D., additional, Spillantini, Maria Grazia, additional, Morris, Huw R., additional, Rizzu, Patrizia, additional, Heutink, Peter, additional, Snowden, Julie S., additional, Rollinson, Sara, additional, Richardson, Anna, additional, Gerhard, Alexander, additional, Bruni, Amalia C., additional, Maletta, Raffaele, additional, Frangipane, Francesca, additional, Cupidi, Chiara, additional, Bernardi, Livia, additional, Anfossi, Maria, additional, Gallo, Maura, additional, Conidi, Maria Elena, additional, Smirne, Nicoletta, additional, Rademakers, Rosa, additional, Baker, Matt, additional, Dickson, Dennis W., additional, Graff-Radford, Neill R., additional, Petersen, Ronald C., additional, Knopman, David, additional, Josephs, Keith A., additional, Boeve, Bradley F., additional, Parisi, Joseph E., additional, Seeley, William W., additional, Miller, Bruce L., additional, Karydas, Anna M., additional, Rosen, Howard, additional, van Swieten, John C., additional, Dopper, Elise G.P., additional, Seelaar, Harro, additional, Pijnenburg, Yolande A.L., additional, Scheltens, Philip, additional, Logroscino, Giancarlo, additional, Capozzo, Rosa, additional, Novelli, Valeria, additional, Puca, Annibale A., additional, Franceschi, Massimo, additional, Postiglione, Alfredo, additional, Milan, Graziella, additional, Sorrentino, Paolo, additional, Kristiansen, Mark, additional, Chiang, Huei-Hsin, additional, Graff, Caroline, additional, Pasquier, Florence, additional, Rollin, Adeline, additional, Deramecourt, Vincent, additional, Lebert, Florence, additional, Kapogiannis, Dimitrios, additional, Ferrucci, Luigi, additional, Pickering-Brown, Stuart, additional, Singleton, Andrew B., additional, Hardy, John, additional, and Momeni, Parastoo, additional
Published: 2023
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40. MAPT haplotype H1G is associated with increased risk of dementia with Lewy bodies

Author: Labbé, Catherine, Heckman, Michael G., Lorenzo-Betancor, Oswaldo, Soto-Ortolaza, Alexandra I., Walton, Ronald L., Murray, Melissa E., Allen, Mariet, Uitti, Ryan J., Wszolek, Zbigniew K., Smith, Glenn E., Kantarci, Kejal, Knopman, David S., Lowe, Val J., Jack, Clifford R., Jr., Ertekin-Taner, Nilüfer, Hassan, Anhar, Savica, Rodolfo, Petersen, Ronald C., Parisi, Joseph E., Maraganore, Demetrius M., Graff-Radford, Neill R., Ferman, Tanis J., Boeve, Bradley F., Dickson, Dennis W., and Ross, Owen A.
Published: 2016
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41. LRRK2 variation and dementia with Lewy bodies

Author: Heckman, Michael G., Soto-Ortolaza, Alexandra I., Sanchez Contreras, Monica Y., Murray, Melissa E., Pedraza, Otto, Diehl, Nancy N., Walton, Ronald, Labbé, Catherine, Lorenzo-Betancor, Oswaldo, Uitti, Ryan J., van Gerpen, Jay, Ertekin-Taner, Nilüfer, Smith, Glenn E., Kantarci, Kejal, Savica, Rodolfo, Jones, David T., Graff-Radford, Jonathan, Knopman, David S., Lowe, Val J., Jack, Clifford R., Jr., Petersen, Ronald C., Parisi, Joseph E., Rademakers, Rosa, Wszolek, Zbigniew K., Graff-Radford, Neill R., Ferman, Tanis J., Dickson, Dennis W., Boeve, Bradley F., and Ross, Owen A.
Published: 2016
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42. Spt4 selectively regulates the expression of C9orf72 sense and antisense mutant transcripts

Author: Kramer, Nicholas J., Carlomagno, Yari, Zhang, Yong-Jie, Almeida, Sandra, Cook, Casey N., Gendron, Tania F., Prudencio, Mercedes, Van Blitterswijk, Marka, Belzil, Veronique, Couthouis, Julien, Paul, Joseph West, Goodman, Lindsey D., Daughrity, Lillian, Chew, Jeannie, Garrett, Aliesha, Pregent, Luc, Jansen-West, Karen, Tabassian, Lilia J., Rademakers, Rosa, Boylan, Kevin, Graff-Radford, Neill R., Josephs, Keith A., Parisi, Joseph E., Knopman, David S., Petersen, Ronald C., Boeve, Bradley F., Deng, Ning, Feng, Yanan, Cheng, Tzu-Hao, Dickson, Dennis W., Cohen, Stanley N., Bonini, Nancy M., Link, Christopher D., Gao, Fen-Biao, Petrucelli, Leonard, and Gitler, Aaron D.
Published: 2016

43. Plasma sphingolipid changes with autopsy-confirmed Lewy body or Alzheimer's pathology

Author: Savica, Rodolfo, Murray, Melissa E., Persson, Xuan-Mai, Kantarci, Kejal, Parisi, Joseph E., Dickson, Dennis W., Petersen, Ronald C., Ferman, Tanis J., Boeve, Bradley F., and Mielke, Michelle M.
Published: 2016
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44. A large-scale comparison of cortical thickness and volume methods for measuring Alzheimer's disease severity

Author: Schwarz, Christopher G., Gunter, Jeffrey L., Wiste, Heather J., Przybelski, Scott A., Weigand, Stephen D., Ward, Chadwick P., Senjem, Matthew L., Vemuri, Prashanthi, Murray, Melissa E., Dickson, Dennis W., Parisi, Joseph E., Kantarci, Kejal, Weiner, Michael W., Petersen, Ronald C., and Jack, Clifford R., Jr
Published: 2016
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45. Expanding the spectrum of subacute diencephalic angioencephalopathy

Author: Graffeo, Christopher S., Dawson, Elliot T., Murphy, Meghan E., Black, David F., Parisi, Joseph E., Crum, Brian A., and Meyer, Fredric B.
Published: 2016
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46. β-Amyloid PET and neuropathology in dementia with Lewy bodies

Author: Kantarci, Kejal, Lowe, Val J., Chen, Qin, Przybelski, Scott A., Lesnick, Timothy G., Schwarz, Christopher G., Senjem, Matthew L., Gunter, Jeffrey L., Jack, Clifford R., Jr, Graff-Radford, Jonathan, Jones, David T., Knopman, David S., Graff-Radford, Neill, Ferman, Tanis J., Parisi, Joseph E., Dickson, Dennis W., Petersen, Ronald C., Boeve, Bradley F., and Murray, Melissa E.
Published: 2020
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47. Levodopa-induced dyskinesia in Parkinson disease: A population-based cohort study

Author: Turcano, Pierpaolo, Mielke, Michelle M., Bower, James H., Parisi, Joseph E., Cutsforth-Gregory, Jeremy K., Ahlskog, J. Eric, and Savica, Rodolfo
Published: 2018
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48. Creating the Pick’s disease International Consortium: Association study ofMAPTH2 haplotype with risk of Pick’s disease

Author: Valentino, Rebecca R, primary, Scotton, William J, additional, Roemer, Shanu F, additional, Lashley, Tammaryn, additional, Heckman, Michael G, additional, Shoai, Maryam, additional, Martinez-Carrasco, Alejandro, additional, Tamvaka, Nicole, additional, Walton, Ronald L, additional, Baker, Matthew C, additional, Macpherson, Hannah L, additional, Real, Raquel, additional, Soto-Beasley, Alexandra I, additional, Mok, Kin, additional, Revesz, Tamas, additional, Warner, Thomas T, additional, Jaunmuktane, Zane, additional, Boeve, Bradley F, additional, Christopher, Elizabeth A, additional, DeTure, Michael, additional, Duara, Ranjan, additional, Graff-Radford, Neill R, additional, Josephs, Keith A, additional, Knopman, David S, additional, Koga, Shunsuke, additional, Murray, Melissa E, additional, Lyons, Kelly E, additional, Pahwa, Rajesh, additional, Parisi, Joseph E, additional, Petersen, Ronald C, additional, Whitwell, Jennifer, additional, Grinberg, Lea T, additional, Miller, Bruce, additional, Schlereth, Athena, additional, Seeley, William W, additional, Spina, Salvatore, additional, Grossman, Murray, additional, Irwin, David J, additional, Lee, Edward B, additional, Suh, EunRan, additional, Trojanowski, John Q, additional, Van Deerlin, Vivianna M, additional, Wolk, David A, additional, Connors, Theresa R, additional, Dooley, Patrick M, additional, Frosch, Matthew P, additional, Oakley, Derek H, additional, Aldecoa, Iban, additional, Balasa, Mircea, additional, Gelpi, Ellen, additional, Borrego-Écija, Sergi, additional, de Eugenio Huélamo, Rosa Maria, additional, Gascon-Bayarri, Jordi, additional, Sánchez-Valle, Raquel, additional, Sanz-Cartagena, Pilar, additional, Piñol-Ripoll, Gerard, additional, Molina-Porcel, Laura, additional, Bigio, Eileen H, additional, Flanagan, Margaret E, additional, Gefen, Tamar, additional, Rogalski, Emily J, additional, Weintraub, Sandra, additional, Redding-Ochoa, Javier, additional, Chang, Koping, additional, Troncoso, Juan C, additional, Prokop, Stefan, additional, Newell, Kathy L, additional, Ghetti, Bernardino, additional, Jones, Matthew, additional, Richardson, Anna, additional, Robinson, Andrew C, additional, Roncaroli, Federico, additional, Snowden, Julie, additional, Allinson, Kieren, additional, Green, Oliver, additional, Rowe, James B, additional, Singh, Poonam, additional, Beach, Thomas G, additional, Serrano, Geidy E, additional, Flowers, Xena E, additional, Goldman, James E, additional, Heaps, Allison C, additional, Leskinen, Sandra P, additional, Teich, Andrew F, additional, Black, Sandra E, additional, Keith, Julia L, additional, Masellis, Mario, additional, Bodi, Istvan, additional, King, Andrew, additional, Sarraj, Safa-Al, additional, Troakes, Claire, additional, Halliday, Glenda M, additional, Hodges, John R, additional, Kril, Jillian J, additional, Kwok, John B, additional, Piguet, Olivier, additional, Gearing, Marla, additional, Arzberger, Thomas, additional, Roeber, Sigrun, additional, Attems, Johannes, additional, Morris, Christopher M, additional, Thomas, Alan J, additional, Evers, Bret M., additional, White, Charles L, additional, Mechawar, Naguib, additional, Sieben, Anne A, additional, Cras, Patrick P, additional, De Vil, Bart B, additional, De Deyn, Peter Paul P.P., additional, Duyckaerts, Charles, additional, Ber, Isabelle Le, additional, Seihean, Danielle, additional, Turbant-Leclere, Sabrina, additional, MacKenzie, Ian R, additional, McLean, Catriona, additional, Cykowski, Matthew D, additional, Ervin, John F, additional, Wang, Shih-Hsiu J, additional, Graff, Caroline, additional, Nennesmo, Inger, additional, Nagra, Rashed M, additional, Riehl, James, additional, Kovacs, Gabor G, additional, Giaccone, Giorgio, additional, Nacmias, Benedetta, additional, Neumann, Manuela, additional, Ang, Lee-Cyn, additional, Finger, Elizabeth C, additional, Blauwendraat, Cornelis, additional, Nalls, Mike A, additional, Singleton, Andrew B, additional, Vitale, Dan, additional, Cunha, Cristina, additional, Carvalho, Agostinho, additional, Wszolek, Zbigniew K, additional, Morris, Huw R, additional, Rademakers, Rosa, additional, Hardy, John A, additional, Dickson, Dennis W, additional, Rohrer, Jonathan D, additional, and Ross, Owen A, additional
Published: 2023
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49. Pittsburgh compound B (PiB) PET imaging of meningioma and other intracranial tumors

Author: Johnson, Derek R., Hunt, Christopher H., Nathan, Mark A., Parisi, Joseph E., Boeve, Bradley F., Murray, Melissa E., Knopman, David S., Jack, Jr., Clifford R., Petersen, Ronald C., Lowe, Val J., and Johnson, Geoffrey B.
Published: 2017
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50. In-depth clinico-pathological examination of RNA foci in a large cohort of C9ORF72 expansion carriers

Author: DeJesus-Hernandez, Mariely, Finch, NiCole A., Wang, Xue, Gendron, Tania F., Bieniek, Kevin F., Heckman, Michael G., Vasilevich, Aliaksei, Murray, Melissa E., Rousseau, Linda, Weesner, Rachael, Lucido, Anthony, Parsons, Meeia, Chew, Jeannie, Josephs, Keith A., Parisi, Joseph E., Knopman, David S., Petersen, Ronald C., Boeve, Bradley F., Graff-Radford, Neill R., de Boer, Jan, Asmann, Yan W., Petrucelli, Leonard, Boylan, Kevin B., Dickson, Dennis W., van Blitterswijk, Marka, and Rademakers, Rosa
Published: 2017
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