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1. Investigation of the genetic aetiology of Lewy body diseases with and without dementia

Author: Wu, Lesley Yue, Real, Raquel, Martinez-Carrasco, Alejandro, Chia, Ruth, Lawton, Michael A, Shoai, Maryam, Bresner, Catherine, Blauwendraat, Cornelis, Singleton, Andrew B, Ryten, Mina, Abramzon, Yevgeniya, Ahmed, Sarah, Alba, Camille, Albert, Marilyn S, Bacikova, Dagmar, Barrett, Matthew J, Beach, Thomas G, Bennett, David A, Besser, Lilah M, Bigio, Eileen H, Boeve, Bradley F, Bohannan, Ryan C, Caraway, Chad A, Palma, Jose-Alberto, Dalgard, Clifton L, Dickson, Dennis, Ding, Jinhui, Faber, Kelley, Ferman, Tanis, Ferrucci, Luigi, Flanagan, Margaret E, Foroud, Tatiana M, Ghetti, Bernardino, Gibbs, J Raphael, Goate, Alison, Goldstein, David, Graff-Radford, Neill R, Hu, Heng-Chen, Hupalo, Daniel, Kaiser, Scott M, Kaufmann, Horacio, Kim, Ronald C, Klein, Gregory, Kukull, Walter, Kuzma, Amanda, Leverenz, James, Lopez, Grisel, Mao, Qinwen, Martinez-McGrath, Elisa, Masliah, Eliezer, Monuki, Ed, Newell, Kathy L, Norcliffe-Kaufmann, Lucy, Perkins, Matthew, Pletnikova, Olga, Renton, Alan E, Resnick, Susan M, Ross, Owen A, Sabir, Marya S, Scherzer, Clemens R, Scholz, Sonja W, Serrano, Geidy, Shakkotai, Vikram, Sidransky, Ellen, Tanaka, Toshiko, Tayebi, Nahid, Traynor, Bryan J, Troncoso, Juan C, Viollet, Coralie, Walton, Ronald L, Woltjer, Randy, Wszolek, Zbigniew K, Black, Sandra E, Gan-Or, Ziv, Keith, Julia, Masellis, Mario, Rogaeva, Ekaterina, Aarsland, Dag, Al-Sarraj, Safa, Attems, Johannes, Ferrari, Raffaele, Gentleman, Steve, Hardy, John A, Hodges, Angela K, Love, Seth, McKeith, Ian, Morris, Christopher M, Morris, Huw R, Palmer, Laura, Pickering-Brown, Stuart, Reynolds, Regina H, Thomas, Alan J, Tilley, Bension S, Troakes, Claire, Brett, Francesca, Brice, Alexis, and Duyckaerts, Charles
Subjects: Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Neurodegenerative, Genetics, Prevention, Aging, Lewy Body Dementia, Brain Disorders, Dementia, Alzheimer's Disease Related Dementias (ADRD), Parkinson's Disease, Human Genome, Acquired Cognitive Impairment, Clinical Research, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), 2.1 Biological and endogenous factors, Neurological, International Lewy Body Dementia Genomics Consortium, APOE, Lewy body diseases, dementia, genome-wide association studies, Clinical sciences, Biological psychology
Abstract: Up to 80% of Parkinson's disease patients develop dementia, but time to dementia varies widely from motor symptom onset. Dementia with Lewy bodies presents with clinical features similar to Parkinson's disease dementia, but cognitive impairment precedes or coincides with motor onset. It remains controversial whether dementia with Lewy bodies and Parkinson's disease dementia are distinct conditions or represent part of a disease spectrum. The biological mechanisms underlying disease heterogeneity, in particular the development of dementia, remain poorly understood, but will likely be the key to understanding disease pathways and, ultimately, therapy development. Previous genome-wide association studies in Parkinson's disease and dementia with Lewy bodies/Parkinson's disease dementia have identified risk loci differentiating patients from controls. We collated data for 7804 patients of European ancestry from Tracking Parkinson's, The Oxford Discovery Cohort, and Accelerating Medicine Partnership-Parkinson's Disease Initiative. We conducted a discrete phenotype genome-wide association study comparing Lewy body diseases with and without dementia to decode disease heterogeneity by investigating the genetic drivers of dementia in Lewy body diseases. We found that risk allele rs429358 tagging APOEe4 increases the odds of developing dementia, and that rs7668531 near the MMRN1 and SNCA-AS1 genes and an intronic variant rs17442721 tagging LRRK2 G2019S on chromosome 12 are protective against dementia. These results should be validated in autopsy-confirmed cases in future studies.
Published: 2024

2. Prevalence, distribution, and severity of cerebral amyloid angiopathy differ between Lewy body diseases and Alzheimer’s disease

Author: Walker, Lauren, Simpson, Harry, Thomas, Alan J., and Attems, Johannes
Published: 2024
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3. Genome-wide structural variant analysis identifies risk loci for non-Alzheimer’s dementias

Author: Kaivola, Karri, Chia, Ruth, Ding, Jinhui, Rasheed, Memoona, Fujita, Masashi, Menon, Vilas, Walton, Ronald L, Collins, Ryan L, Billingsley, Kimberley, Brand, Harrison, Talkowski, Michael, Zhao, Xuefang, Dewan, Ramita, Stark, Ali, Ray, Anindita, Solaiman, Jerez, Pilar Alvarez, Malik, Laksh, Dawson, Ted M, Rosenthal, Liana S, Albert, Marilyn S, Pletnikova, Olga, Troncoso, Juan C, Masellis, Mario, Keith, Julia, Black, Sandra E, Ferrucci, Luigi, Resnick, Susan M, Tanaka, Toshiko, Soltis, Anthony R, Viollet, Coralie, Sukumar, Gauthaman, Alba, Camille, Lott, Nathaniel, Martinez, Elisa McGrath, Tuck, Meila, Singh, Jatinder, Bacikova, Dagmar, Zhang, Xijun, Hupalo, Daniel N, Adeleye, Adelani, Wilkerson, Matthew D, Pollard, Harvey B, Dalgard, Clifton L, Gan-Or, Ziv, Rogaeva, Ekaterina, Brice, Alexis, Lesage, Suzanne, Xiromerisiou, Georgia, Calvo, Andrea, Canosa, Antonio, Chio, Adriano, Logroscino, Giancarlo, Mora, Gabriele, Krüger, Reijko, May, Patrick, Alcolea, Daniel, Clarimon, Jordi, Fortea, Juan, Gonzalez-Aramburu, Isabel, Infante, Jon, Lage, Carmen, Lleó, Alberto, Pastor, Pau, Sanchez-Juan, Pascual, Brett, Francesca, Aarsland, Dag, Al-Sarraj, Safa, Attems, Johannes, Gentleman, Steve, Hardy, John A, Hodges, Angela K, Love, Seth, McKeith, Ian G, Morris, Christopher M, Morris, Huw R, Palmer, Laura, Pickering-Brown, Stuart, Ryten, Mina, Thomas, Alan J, Troakes, Claire, Barrett, Matthew J, Beach, Thomas G, Bekris, Lynn M, Bennett, David A, Boeve, Bradley F, Dickson, Dennis W, Faber, Kelley, Ferman, Tanis, Flanagan, Margaret E, Foroud, Tatiana M, Ghetti, Bernardino, and Gibbs, J Raphael
Subjects: Biological Sciences, Genetics, Brain Disorders, Dementia, ALS, Rare Diseases, Neurodegenerative, Neurosciences, Human Genome, Frontotemporal Dementia (FTD), Alzheimer's Disease, Alzheimer's Disease Related Dementias (ADRD), Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Aging, Aetiology, 2.1 Biological and endogenous factors, Neurological, American Genome Center, International LBD Genomics Consortium, International ALS/FTD Consortium, PROSPECT Consortium, Lewy body dementia, amyotrophic lateral sclerosis, case-control study, frontotemporal dementia, genome-wide association study, non–Alzheimer's dementia, resource, structural variant
Abstract: We characterized the role of structural variants, a largely unexplored type of genetic variation, in two non-Alzheimer's dementias, namely Lewy body dementia (LBD) and frontotemporal dementia (FTD)/amyotrophic lateral sclerosis (ALS). To do this, we applied an advanced structural variant calling pipeline (GATK-SV) to short-read whole-genome sequence data from 5,213 European-ancestry cases and 4,132 controls. We discovered, replicated, and validated a deletion in TPCN1 as a novel risk locus for LBD and detected the known structural variants at the C9orf72 and MAPT loci as associated with FTD/ALS. We also identified rare pathogenic structural variants in both LBD and FTD/ALS. Finally, we assembled a catalog of structural variants that can be mined for new insights into the pathogenesis of these understudied forms of dementia.
Published: 2023

4. LATE-NC staging in routine neuropathologic diagnosis: an update

Author: Nelson, Peter T, Lee, Edward B, Cykowski, Matthew D, Alafuzoff, Irina, Arfanakis, Konstantinos, Attems, Johannes, Brayne, Carol, Corrada, Maria M, Dugger, Brittany N, Flanagan, Margaret E, Ghetti, Bernardino, Grinberg, Lea T, Grossman, Murray, Grothe, Michel J, Halliday, Glenda M, Hasegawa, Masato, Hokkanen, Suvi RK, Hunter, Sally, Jellinger, Kurt, Kawas, Claudia H, Keene, C Dirk, Kouri, Naomi, Kovacs, Gabor G, Leverenz, James B, Latimer, Caitlin S, Mackenzie, Ian R, Mao, Qinwen, McAleese, Kirsty E, Merrick, Richard, Montine, Thomas J, Murray, Melissa E, Myllykangas, Liisa, Nag, Sukriti, Neltner, Janna H, Newell, Kathy L, Rissman, Robert A, Saito, Yuko, Sajjadi, S Ahmad, Schwetye, Katherine E, Teich, Andrew F, Thal, Dietmar R, Tomé, Sandra O, Troncoso, Juan C, Wang, Shih-Hsiu J, White, Charles L, Wisniewski, Thomas, Yang, Hyun-Sik, Schneider, Julie A, Dickson, Dennis W, and Neumann, Manuela
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Neurosciences, Genetics, Acquired Cognitive Impairment, Neurodegenerative, Brain Disorders, Dementia, Rare Diseases, Neurological, Humans, Alzheimer Disease, Frontotemporal Dementia, Amyotrophic Lateral Sclerosis, DNA-Binding Proteins, Processes, NCI, TDP-43, FTD, Stages, Hippocampal sclerosis, Neuroanatomy, Aging, Neurology & Neurosurgery
Abstract: An international consensus report in 2019 recommended a classification system for limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC). The suggested neuropathologic staging system and nomenclature have proven useful for autopsy practice and dementia research. However, some issues remain unresolved, such as cases with unusual features that do not fit with current diagnostic categories. The goal of this report is to update the neuropathologic criteria for the diagnosis and staging of LATE-NC, based primarily on published data. We provide practical suggestions about how to integrate available genetic information and comorbid pathologies [e.g., Alzheimer's disease neuropathologic changes (ADNC) and Lewy body disease]. We also describe recent research findings that have enabled more precise guidance on how to differentiate LATE-NC from other subtypes of TDP-43 pathology [e.g., frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS)], and how to render diagnoses in unusual situations in which TDP-43 pathology does not follow the staging scheme proposed in 2019. Specific recommendations are also made on when not to apply this diagnostic term based on current knowledge. Neuroanatomical regions of interest in LATE-NC are described in detail and the implications for TDP-43 immunohistochemical results are specified more precisely. We also highlight questions that remain unresolved and areas needing additional study. In summary, the current work lays out a number of recommendations to improve the precision of LATE-NC staging based on published reports and diagnostic experience.
Published: 2023

5. Regional AT-8 reactive tau species correlate with intracellular Aβ levels in cases of low AD neuropathologic change

Author: Malik, Nauman, Miah, Mohi-Uddin, Galgani, Alessandro, McAleese, Kirsty, Walker, Lauren, LeBeau, Fiona E., Attems, Johannes, Outeiro, Tiago F., Thomas, Alan, and Koss, David J.
Published: 2024
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6. Common Variants Near ZIC1 and ZIC4 in Autopsy-Confirmed Multiple System Atrophy.

Author: Hopfner, Franziska, Tietz, Anja, Ruf, Viktoria, Ross, Owen, Koga, Shunsuke, Dickson, Dennis, Aguzzi, Adriano, Attems, Johannes, Beach, Thomas, Beller, Allison, Cheshire, William, van Deerlin, Vivianna, Deuschl, Günther, Duyckaerts, Charles, Ellinghaus, David, Evsyukov, Valentin, Flanagan, Margaret, Franke, Andre, Frosch, Matthew, Gearing, Marla, Gelpi, Ellen, van Gerpen, Jay, Ghetti, Bernardino, Glass, Jonathan, Halliday, Glenda, Helbig, Ingo, Höllerhage, Matthias, Huitinga, Inge, Irwin, David, Keene, Dirk, Kovacs, Gabor, Lee, Edward, Levin, Johannes, Martí, Maria, Mackenzie, Ian, McKeith, Ian, Mclean, Catriona, Mollenhauer, Brit, Neumann, Manuela, Newell, Kathy, Pantelyat, Alex, Pendziwiat, Manuela, Peters, Annette, Molina Porcel, Laura, Rabano, Alberto, Matěj, Radoslav, Rajput, Alex, Rajput, Ali, Reimann, Regina, Scott, William, Selvackadunco, Sashika, Simuni, Tanya, Stadelmann, Christine, Svenningsson, Per, Thomas, Alan, Trenkwalder, Claudia, Troakes, Claire, Trojanowski, John, Uitti, Ryan, White, Charles, Wszolek, Zbigniew, Xie, Tao, Ximelis, Teresa, Yebenes, Justo, Müller, Ulrich, Schellenberg, Gerard, Herms, Jochen, Kuhlenbäumer, Gregor, Höglinger, Günter, Grinberg, Lea, Seeley, William, and Desplats, Paula
Subjects: ZIC1, ZIC4, autopsy-confirmed, genome-wide association study, multiple system atrophy, Autoantibodies, Autopsy, Genome-Wide Association Study, Humans, Multiple System Atrophy, Nerve Tissue Proteins, Olivopontocerebellar Atrophies, Striatonigral Degeneration, Transcription Factors, alpha-Synuclein
Abstract: BACKGROUND: Multiple System Atrophy is a rare neurodegenerative disease with alpha-synuclein aggregation in glial cytoplasmic inclusions and either predominant olivopontocerebellar atrophy or striatonigral degeneration, leading to dysautonomia, parkinsonism, and cerebellar ataxia. One prior genome-wide association study in mainly clinically diagnosed patients with Multiple System Atrophy failed to identify genetic variants predisposing for the disease. OBJECTIVE: Since the clinical diagnosis of Multiple System Atrophy yields a high rate of misdiagnosis when compared to the neuropathological gold standard, we studied only autopsy-confirmed cases. METHODS: We studied common genetic variations in Multiple System Atrophy cases (N = 731) and controls (N = 2898). RESULTS: The most strongly disease-associated markers were rs16859966 on chromosome 3, rs7013955 on chromosome 8, and rs116607983 on chromosome 4 with P-values below 5 × 10-6 , all of which were supported by at least one additional genotyped and several imputed single nucleotide polymorphisms. The genes closest to the chromosome 3 locus are ZIC1 and ZIC4 encoding the zinc finger proteins of cerebellum 1 and 4 (ZIC1 and ZIC4). INTERPRETATION: Since mutations of ZIC1 and ZIC4 and paraneoplastic autoantibodies directed against ZIC4 are associated with severe cerebellar dysfunction, we conducted immunohistochemical analyses in brain tissue of the frontal cortex and the cerebellum from 24 Multiple System Atrophy patients. Strong immunohistochemical expression of ZIC4 was detected in a subset of neurons of the dentate nucleus in all healthy controls and in patients with striatonigral degeneration, whereas ZIC4-immunoreactive neurons were significantly reduced inpatients with olivopontocerebellar atrophy. These findings point to a potential ZIC4-mediated vulnerability of neurons in Multiple System Atrophy. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Published: 2022

7. Differential Vulnerability of Hippocampal Subfields in Primary Age-Related Tauopathy and Chronic Traumatic Encephalopathy.

Author: Farrell, Kurt, Iida, Megan A, Cherry, Jonathan D, Casella, Alicia, Stein, Thor D, Bieniek, Kevin F, Walker, Jamie M, Richardson, Timothy E, White, Charles L, Alvarez, Victor E, Huber, Bertrand R, Dickson, Dennis W, Insausti, Ricardo, Dams-O'Connor, Kristen, Vonsattel, Jean-Paul, Teich, Andy F, Gearing, Marla, Glass, Jonathan, Troncoso, Juan C, Frosch, Matthew P, Hyman, Bradley T, Murray, Melissa E, Attems, Johannes, Flanagan, Margaret E, Mao, Qinwen, Mesulam, M-Marsel, Weintraub, Sandra, Woltjer, Randy L, Pham, Thao, Kofler, Julia, Schneider, Julie A, Yu, Lei, Purohit, Dushyant P, Haroutunian, Vahram, Hof, Patrick R, Gandy, Sam, Sano, Mary, Beach, Thomas G, Poon, Wayne, Kawas, Claudia H, Corrada, María M, Rissman, Robert A, Metcalf, Jeff, Shuldberg, Sara, Salehi, Bahar, Nelson, Peter T, Trojanowski, John Q, Lee, Edward B, Wolk, David A, McMillan, Corey T, Keene, C Dirk, Latimer, Caitlin S, Montine, Thomas J, Kovacs, Gabor G, Lutz, Mirjam I, Fischer, Peter, Perrin, Richard J, Cairns, Nigel J, McKee, Ann C, and Crary, John F
Subjects: Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Frontotemporal Dementia (FTD), Acquired Cognitive Impairment, Aging, Brain Disorders, Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease, Neurodegenerative, Aetiology, 2.1 Biological and endogenous factors, Chronic Traumatic Encephalopathy, Hippocampus, Humans, Neurofibrillary Tangles, Tauopathies, tau Proteins, Chronic traumatic encephalopathy, Primary age-related tauopathy, Repetitive head impacts, Tauopathy, Part Working Group, Neurology & Neurosurgery, Clinical sciences
Abstract: Chronic traumatic encephalopathy (CTE) is a tauopathy associated with repetitive mild head impacts characterized by perivascular hyperphosphorylated tau (p-tau) in neurofibrillary tangles (NFTs) and neurites in the depths of the neocortical sulci. In moderate to advanced CTE, NFTs accumulate in the hippocampus, potentially overlapping neuroanatomically with primary age-related tauopathy (PART), an age-related tauopathy characterized by Alzheimer disease-like tau pathology in the hippocampus devoid of amyloid plaques. We measured p-tau burden using positive-pixel counts on immunohistochemically stained and neuroanatomically segmented hippocampal tissue. Subjects with CTE had a higher total p-tau burden than PART subjects in all sectors (p = 0.005). Within groups, PART had significantly higher total p-tau burden in CA1/subiculum compared to CA3 (p = 0.02) and CA4 (p = 0.01) and total p-tau burden in CA2 trended higher than CA4 (p = 0.06). In CTE, total p-tau burden in CA1/subiculum was significantly higher than in the dentate gyrus; and CA2 also trended higher than dentate gyrus (p = 0.01, p = 0.06). When controlling for p-tau burden across the entire hippocampus, CA3 and CA4 had significantly higher p-tau burden in CTE than PART (p
Published: 2022

8. Frequency of LATE neuropathologic change across the spectrum of Alzheimer’s disease neuropathology: combined data from 13 community-based or population-based autopsy cohorts

Author: Nelson, Peter T, Brayne, Carol, Flanagan, Margaret E, Abner, Erin L, Agrawal, Sonal, Attems, Johannes, Castellani, Rudolph J, Corrada, Maria M, Cykowski, Matthew D, Di, Jing, Dickson, Dennis W, Dugger, Brittany N, Ervin, John F, Fleming, Jane, Graff-Radford, Jonathan, Grinberg, Lea T, Hokkanen, Suvi RK, Hunter, Sally, Kapasi, Alifiya, Kawas, Claudia H, Keage, Hannah AD, Keene, C Dirk, Kero, Mia, Knopman, David S, Kouri, Naomi, Kovacs, Gabor G, Labuzan, Sydney A, Larson, Eric B, Latimer, Caitlin S, Leite, Renata EP, Matchett, Billie J, Matthews, Fiona E, Merrick, Richard, Montine, Thomas J, Murray, Melissa E, Myllykangas, Liisa, Nag, Sukriti, Nelson, Ruth S, Neltner, Janna H, Nguyen, Aivi T, Petersen, Ronald C, Polvikoski, Tuomo, Reichard, R Ross, Rodriguez, Roberta D, Suemoto, Claudia K, Wang, Shih-Hsiu J, Wharton, Stephen B, White, Lon, and Schneider, Julie A
Subjects: Biomedical and Clinical Sciences, Neurosciences, Clinical Research, Alzheimer's Disease, Acquired Cognitive Impairment, Aging, Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Alzheimer's Disease Related Dementias (ADRD), Dementia, Behavioral and Social Science, 2.1 Biological and endogenous factors, Aetiology, Neurological, Aged, 80 and over, Alzheimer Disease, Amyloid, Autopsy, DNA-Binding Proteins, Frontotemporal Dementia, Humans, Male, Nervous System Diseases, Plaque, Amyloid, ADRD, Tau, NFT, Nondemented, Oldest-old, Epidemiology, APOE, ROS-MAP, Vantaa 85+, HAAS, CFAS, CC75C, The 90+study, ACT, VITA, Nun study, Biobank for aging studies, Mayo clinic study of aging, The 90 + study, Vantaa 85 + , Clinical Sciences, Neurology & Neurosurgery
Abstract: Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) and Alzheimer's disease neuropathologic change (ADNC) are each associated with substantial cognitive impairment in aging populations. However, the prevalence of LATE-NC across the full range of ADNC remains uncertain. To address this knowledge gap, neuropathologic, genetic, and clinical data were compiled from 13 high-quality community- and population-based longitudinal studies. Participants were recruited from United States (8 cohorts, including one focusing on Japanese-American men), United Kingdom (2 cohorts), Brazil, Austria, and Finland. The total number of participants included was 6196, and the average age of death was 88.1 years. Not all data were available on each individual and there were differences between the cohorts in study designs and the amount of missing data. Among those with known cognitive status before death (n = 5665), 43.0% were cognitively normal, 14.9% had MCI, and 42.4% had dementia-broadly consistent with epidemiologic data in this age group. Approximately 99% of participants (n = 6125) had available CERAD neuritic amyloid plaque score data. In this subsample, 39.4% had autopsy-confirmed LATE-NC of any stage. Among brains with "frequent" neuritic amyloid plaques, 54.9% had comorbid LATE-NC, whereas in brains with no detected neuritic amyloid plaques, 27.0% had LATE-NC. Data on LATE-NC stages were available for 3803 participants, of which 25% had LATE-NC stage > 1 (associated with cognitive impairment). In the subset of individuals with Thal Aβ phase = 0 (lacking detectable Aβ plaques), the brains with LATE-NC had relatively more severe primary age-related tauopathy (PART). A total of 3267 participants had available clinical data relevant to frontotemporal dementia (FTD), and none were given the clinical diagnosis of definite FTD nor the pathological diagnosis of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). In the 10 cohorts with detailed neurocognitive assessments proximal to death, cognition tended to be worse with LATE-NC across the full spectrum of ADNC severity. This study provided a credible estimate of the current prevalence of LATE-NC in advanced age. LATE-NC was seen in almost 40% of participants and often, but not always, coexisted with Alzheimer's disease neuropathology.
Published: 2022

9. Genetic evaluation of dementia with Lewy bodies implicates distinct disease subgroups.

Author: Kaivola, Karri, Shah, Zalak, Chia, Ruth, Black, Sandra E, Gan-Or, Ziv, Keith, Julia, Masellis, Mario, Rogaeva, Ekaterina, Brice, Alexis, Lesage, Suzanne, Xiromerisiou, Georgia, Calvo, Andrea, Canosa, Antonio, Chio, Adriano, Logroscino, Giancarlo, Mora, Gabriele, Krüger, Reijko, May, Patrick, Alcolea, Daniel, Clarimon, Jordi, Fortea, Juan, Gonzalez-Aramburu, Isabel, Infante, Jon, Lage, Carmen, Lleó, Alberto, Pastor, Pau, Sanchez-Juan, Pascual, Brett, Francesca, Aarsland, Dag, Al-Sarraj, Safa, Attems, Johannes, Gentleman, Steve, Hardy, John A, Hodges, Angela K, Love, Seth, McKeith, Ian G, Morris, Christopher M, Morris, Huw R, Palmer, Laura, Pickering-Brown, Stuart, Ryten, Mina, Thomas, Alan J, Troakes, Claire, Albert, Marilyn S, Barrett, Matthew J, Beach, Thomas G, Bekris, Lynn M, Bennett, David A, Boeve, Bradley F, Dalgard, Clifton L, Dawson, Ted M, Dickson, Dennis W, Faber, Kelley, Ferman, Tanis, Ferrucci, Luigi, Flanagan, Margaret E, Foroud, Tatiana M, Ghetti, Bernardino, Gibbs, J Raphael, Goate, Alison, Goldstein, David S, Graff-Radford, Neill R, Kaufmann, Horacio, Kukull, Walter A, Leverenz, James B, Mao, Qinwen, Masliah, Eliezer, Monuki, Edwin, Newell, Kathy L, Palma, Jose Alberto, Pletnikova, Olga, Renton, Alan E, Resnick, Susan M, Rosenthal, Liana S, Ross, Owen A, Scherzer, Clemens R, Serrano, Geidy E, Shakkottai, Vikram G, Sidransky, Ellen, Tanaka, Toshiko, Topol, Eric, Torkamani, Ali, Troncoso, Juan C, Woltjer, Randy, Wszolek, Zbigniew K, and Scholz, Sonja W
Subjects: Genetics, Lewy Body Dementia, Neurodegenerative, Aging, Brain Disorders, Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurosciences, Alzheimer's Disease, Acquired Cognitive Impairment, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Neurological, Aged, Alzheimer Disease, Apolipoprotein E4, Genome-Wide Association Study, Humans, Lewy Body Disease, alpha-Synuclein, International LBD Genomics Consortium, APOE, Alzheimer’s disease, co-pathology, dementia with Lewy bodies, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract: The APOE locus is strongly associated with risk for developing Alzheimer's disease and dementia with Lewy bodies. In particular, the role of the APOE ε4 allele as a putative driver of α-synuclein pathology is a topic of intense debate. Here, we performed a comprehensive evaluation in 2466 dementia with Lewy bodies cases versus 2928 neurologically healthy, aged controls. Using an APOE-stratified genome-wide association study approach, we found that GBA is associated with risk for dementia with Lewy bodies in patients without APOE ε4 (P = 6.58 × 10-9, OR = 3.41, 95% CI = 2.25-5.17), but not with dementia with Lewy bodies with APOE ε4 (P = 0.034, OR = 1.87, 95%, 95% CI = 1.05-3.37). We then divided 495 neuropathologically examined dementia with Lewy bodies cases into three groups based on the extent of concomitant Alzheimer's disease co-pathology: pure dementia with Lewy bodies (n = 88), dementia with Lewy bodies with intermediate Alzheimer's disease co-pathology (n = 66) and dementia with Lewy bodies with high Alzheimer's disease co-pathology (n = 341). In each group, we tested the association of the APOE ε4 against the 2928 neurologically healthy controls. Our examination found that APOE ε4 was associated with dementia with Lewy bodies + Alzheimer's disease (P = 1.29 × 10-32, OR = 4.25, 95% CI = 3.35-5.39) and dementia with Lewy bodies + intermediate Alzheimer's disease (P = 0.0011, OR = 2.31, 95% CI = 1.40-3.83), but not with pure dementia with Lewy bodies (P = 0.31, OR = 0.75, 95% CI = 0.43-1.30). In conclusion, although deep clinical data were not available for these samples, our findings do not support the notion that APOE ε4 is an independent driver of α-synuclein pathology in pure dementia with Lewy bodies, but rather implicate GBA as the main risk gene for the pure dementia with Lewy bodies subgroup.
Published: 2022

10. MAPT H2 haplotype and risk of Pick's disease in the Pick's disease International Consortium: a genetic association study

Author: Warner, Thomas T, Jaunmuktane, Zane, Boeve, Bradley F, Duara, Ranjan, Graff-Radford, Neill R, Josephs, Keith A, Knopman, David S, Koga, Shunsuke, Murray, Melissa E, Lyons, Kelly E, Pahwa, Rajesh, Petersen, Ronald C, Whitwell, Jennifer L, Grinberg, Lea T, Miller, Bruce, Schlereth, Athena, Spina, Salvatore, Grossman, Murray, Irwin, David J, Suh, EunRan, Trojanowski, John Q, Van Deerlin, Vivianna M, Wolk, David A, Connors, Theresa R, Dooley, Patrick M, Oakley, Derek H, Aldecoa, Iban, Balasa, Mircea, Gelpi, Ellen, Borrego-Écija, Sergi, Gascon-Bayarri, Jordi, Sánchez-Valle, Raquel, Sanz-Cartagena, Pilar, Piñol-Ripoll, Gerard, Bigio, Eileen H, Flanagan, Margaret E, Rogalski, Emily J, Weintraub, Sandra, Schneider, Julie A, Peng, Lihua, Zhu, Xiongwei, Chang, Koping, Troncoso, Juan C, Prokop, Stefan, Newell, Kathy L, Jones, Matthew, Richardson, Anna, Roncaroli, Federico, Snowden, Julie, Allinson, Kieren, Singh, Poonam, Serrano, Geidy E, Flowers, Xena E, Goldman, James E, Heaps, Allison C, Leskinen, Sandra P, Black, Sandra E, Masellis, Mario, King, Andrew, Al-Sarraj, Safa, Troakes, Claire, Hodges, John R, Kril, Jillian J, Kwok, John B, Piguet, Olivier, Roeber, Sigrun, Attems, Johannes, Thomas, Alan J, Evers, Bret M., Bieniek, Kevin F, Sieben, Anne A, Cras, Patrick P, De Vil, Bart B, Bird, Thomas, Castellani, Rudolph J, Chaffee, Ann, Franklin, Erin, Haroutunian, Vahram, Jacobsen, Max, Keene, Dirk, Latimer, Caitlin S, Metcalf, Jeff, Perrin, Richard J, Purohit, Dushyant P, Rissman, Robert A, Schantz, Aimee, Walker, Jamie, De Deyn, Peter P, Duyckaerts, Charles, Le Ber, Isabelle, Seilhean, Danielle, Turbant-Leclere, Sabrina, Ervin, John F, Nennesmo, Inger, Riehl, James, Nacmias, Benedetta, Finger, Elizabeth C, Blauwendraat, Cornelis, Nalls, Mike A, Singleton, Andrew B, Vitale, Dan, Cunha, Cristina, Wszolek, Zbigniew K, Valentino, Rebecca R, Scotton, William J, Roemer, Shanu F, Lashley, Tammaryn, Heckman, Michael G, Shoai, Maryam, Martinez-Carrasco, Alejandro, Tamvaka, Nicole, Walton, Ronald L, Baker, Matthew C, Macpherson, Hannah L, Real, Raquel, Soto-Beasley, Alexandra I, Mok, Kin, Revesz, Tamas, Christopher, Elizabeth A, DeTure, Michael, Seeley, William W, Lee, Edward B, Frosch, Matthew P, Molina-Porcel, Laura, Gefen, Tamar, Redding-Ochoa, Javier, Ghetti, Bernardino, Robinson, Andrew C, Kobylecki, Christopher, Rowe, James B, Beach, Thomas G, Teich, Andrew F, Keith, Julia L, Bodi, Istvan, Halliday, Glenda M, Gearing, Marla, Arzberger, Thomas, Morris, Christopher M, White, Charles L, 3rd, Mechawar, Naguib, Boluda, Susana, MacKenzie, Ian R, McLean, Catriona, Cykowski, Matthew D, Wang, Shih-Hsiu J, Graff, Caroline, Nagra, Rashed M, Kovacs, Gabor G, Giaccone, Giorgio, Neumann, Manuela, Ang, Lee-Cyn, Carvalho, Agostinho, Morris, Huw R, Rademakers, Rosa, Hardy, John A, Dickson, Dennis W, Rohrer, Jonathan D, and Ross, Owen A
Published: 2024
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11. Genome-wide association study and functional validation implicates JADE1 in tauopathy

Author: Farrell, Kurt, Kim, SoongHo, Han, Natalia, Iida, Megan A, Gonzalez, Elias M, Otero-Garcia, Marcos, Walker, Jamie M, Richardson, Timothy E, Renton, Alan E, Andrews, Shea J, Fulton-Howard, Brian, Humphrey, Jack, Vialle, Ricardo A, Bowles, Kathryn R, de Paiva Lopes, Katia, Whitney, Kristen, Dangoor, Diana K, Walsh, Hadley, Marcora, Edoardo, Hefti, Marco M, Casella, Alicia, Sissoko, Cheick T, Kapoor, Manav, Novikova, Gloriia, Udine, Evan, Wong, Garrett, Tang, Weijing, Bhangale, Tushar, Hunkapiller, Julie, Ayalon, Gai, Graham, Robert R, Cherry, Jonathan D, Cortes, Etty P, Borukov, Valeriy Y, McKee, Ann C, Stein, Thor D, Vonsattel, Jean-Paul, Teich, Andy F, Gearing, Marla, Glass, Jonathan, Troncoso, Juan C, Frosch, Matthew P, Hyman, Bradley T, Dickson, Dennis W, Murray, Melissa E, Attems, Johannes, Flanagan, Margaret E, Mao, Qinwen, Mesulam, M-Marsel, Weintraub, Sandra, Woltjer, Randy L, Pham, Thao, Kofler, Julia, Schneider, Julie A, Yu, Lei, Purohit, Dushyant P, Haroutunian, Vahram, Hof, Patrick R, Gandy, Sam, Sano, Mary, Beach, Thomas G, Poon, Wayne, Kawas, Claudia H, Corrada, María M, Rissman, Robert A, Metcalf, Jeff, Shuldberg, Sara, Salehi, Bahar, Nelson, Peter T, Trojanowski, John Q, Lee, Edward B, Wolk, David A, McMillan, Corey T, Keene, C Dirk, Latimer, Caitlin S, Montine, Thomas J, Kovacs, Gabor G, Lutz, Mirjam I, Fischer, Peter, Perrin, Richard J, Cairns, Nigel J, Franklin, Erin E, Cohen, Herbert T, Raj, Towfique, Cobos, Inma, Frost, Bess, Goate, Alison, White III, Charles L, and Crary, John F
Subjects: Biomedical and Clinical Sciences, Neurosciences, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Genetics, Dementia, Acquired Cognitive Impairment, Frontotemporal Dementia (FTD), Aging, Alzheimer's Disease, Aetiology, 2.1 Biological and endogenous factors, Neurological, Aged, Aged, 80 and over, Animals, Cohort Studies, Drosophila, Female, Genome-Wide Association Study, Homeodomain Proteins, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Tauopathies, Tumor Suppressor Proteins, Clinical Sciences, Neurology & Neurosurgery
Abstract: Primary age-related tauopathy (PART) is a neurodegenerative pathology with features distinct from but also overlapping with Alzheimer disease (AD). While both exhibit Alzheimer-type temporal lobe neurofibrillary degeneration alongside amnestic cognitive impairment, PART develops independently of amyloid-β (Aβ) plaques. The pathogenesis of PART is not known, but evidence suggests an association with genes that promote tau pathology and others that protect from Aβ toxicity. Here, we performed a genetic association study in an autopsy cohort of individuals with PART (n = 647) using Braak neurofibrillary tangle stage as a quantitative trait. We found some significant associations with candidate loci associated with AD (SLC24A4, MS4A6A, HS3ST1) and progressive supranuclear palsy (MAPT and EIF2AK3). Genome-wide association analysis revealed a novel significant association with a single nucleotide polymorphism on chromosome 4 (rs56405341) in a locus containing three genes, including JADE1 which was significantly upregulated in tangle-bearing neurons by single-soma RNA-seq. Immunohistochemical studies using antisera targeting JADE1 protein revealed localization within tau aggregates in autopsy brains with four microtubule-binding domain repeats (4R) isoforms and mixed 3R/4R, but not with 3R exclusively. Co-immunoprecipitation in post-mortem human PART brain tissue revealed a specific binding of JADE1 protein to four repeat tau lacking N-terminal inserts (0N4R). Finally, knockdown of the Drosophila JADE1 homolog rhinoceros (rno) enhanced tau-induced toxicity and apoptosis in vivo in a humanized 0N4R mutant tau knock-in model, as quantified by rough eye phenotype and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) in the fly brain. Together, these findings indicate that PART has a genetic architecture that partially overlaps with AD and other tauopathies and suggests a novel role for JADE1 as a modifier of neurofibrillary degeneration.
Published: 2022

12. Frontal white matter lesions in Alzheimer’s disease are associated with both small vessel disease and AD-associated cortical pathology

Author: McAleese, Kirsty E, Miah, Mohi, Graham, Sophie, Hadfield, Georgina M, Walker, Lauren, Johnson, Mary, Colloby, Sean J, Thomas, Alan J, DeCarli, Charles, Koss, David, and Attems, Johannes
Subjects: Dementia, Neurodegenerative, Aging, Acquired Cognitive Impairment, Brain Disorders, Neurosciences, Clinical Research, Alzheimer's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), 2.1 Biological and endogenous factors, Aetiology, Neurological, Aged, Aged, 80 and over, Alzheimer Disease, Cerebral Small Vessel Diseases, Female, Frontal Lobe, Humans, Intracranial Arteriosclerosis, Male, Pilot Projects, White Matter, White matter lesion, White matter hyperintensity, Alzheimer's disease, Small vessel disease, Amyloid-beta, Hyperphosphorylated tau, Alzheimer’s disease, Clinical Sciences, Neurology & Neurosurgery
Abstract: Cerebral white matter lesions (WML) encompass axonal loss and demyelination and are assumed to be associated with small vessel disease (SVD)-related ischaemia. However, our previous study in the parietal lobe white matter revealed that WML in Alzheimer's disease (AD) are linked with degenerative axonal loss secondary to the deposition of cortical AD pathology. Furthermore, neuroimaging data suggest that pathomechanisms for the development of WML differ between anterior and posterior lobes with AD-associated degenerative mechanism driving posterior white matter disruption, and both AD-associated degenerative and vascular mechanisms contributed to anterior matter disruption. In this pilot study, we used human post-mortem brain tissue to investigate the composition and aetiology of frontal WML from AD and non-demented controls to determine if frontal WML are SVD-associated and to reveal any regional differences in the pathogenesis of WML. Frontal WML tissue sections from 40 human post-mortem brains (AD, n = 19; controls, n = 21) were quantitatively assessed for demyelination, axonal loss, cortical hyperphosphorylated tau (HPτ) and amyloid-beta (Aβ) burden, and arteriolosclerosis as a measure of SVD. Biochemical assessment included Wallerian degeneration-associated protease calpain and the myelin-associated glycoprotein to proteolipid protein ratio as a measure of ante-mortem ischaemia. Arteriolosclerosis severity was found to be associated with and a significant predictor of frontal WML severity in both AD and non-demented controls. Interesting, frontal axonal loss was also associated with HPτ and calpain levels were associated with increasing Aβ burden in the AD group, suggestive of an additional degenerative influence. To conclude, this pilot data suggest that frontal WML in AD may result from both increased arteriolosclerosis and AD-associated degenerative changes. These preliminary findings in combination with previously published data tentatively indicate regional differences in the aetiology of WML in AD, which should be considered in the clinical diagnosis of dementia subtypes: posterior WML maybe associated with degenerative mechanisms secondary to AD pathology, while anterior WML could be associated with both SVD-associated and degenerative mechanisms.
Published: 2021

13. Genome-wide association study and functional validation implicates JADE1 in tauopathy

Author: Farrell, Kurt, Kim, SoongHo, Han, Natalia, Iida, Megan A, Gonzalez, Elias, Otero-Garcia, Marcos, Walker, Jamie, Richardson, Tim, Renton, Alan E, Andrews, Shea J, Fulton-Howard, Brian, Humphrey, Jack, Vialle, Ricardo A, Bowles, Kathryn R, Whitney, Kristen, Dangoor, Diana K, Marcora, Edoardo, Hefti, Marco M, Casella, Alicia, Sissoko, Cheick, Kapoor, Manav, Novikova, Gloriia, Udine, Evan, Wong, Garrett, Tang, Weijing, Bhangale, Tushar, Hunkapiller, Julie, Ayalon, Gai, Graham, Rob, Cherry, Jonathan D, Cortes, Etty, Borukov, Valeriy, McKee, Ann C, Stein, Thor D, Vonsattel, Jean-Paul, Teich, Andy F, Gearing, Marla, Glass, Jonathan, Troncoso, Juan C, Frosch, Matthew P, Hyman, Bradley T, Dickson, Dennis W, Murray, Melissa E, Attems, Johannes, Flanagan, Margaret E, Mao, Qinwen, Mesulam, M-Marsel, Weintraub, Sandra, Woltjer, Randy, Pham, Thao, Kofler, Julia, Schneider, Julie A, Yu, Lei, Purohit, Dushyant P, Haroutunian, Vahram, Hof, Patrick R, Gandy, Sam, Sano, Mary, Beach, Thomas G, Poon, Wayne, Kawas, Claudia, Corrada, María, Rissman, Robert A, Metcalf, Jeff, Shuldberg, Sara, Salehi, Bahar, Nelson, Peter T, Trojanowski, John Q, Lee, Edward B, Wolk, David A, McMillan, Corey T, Keene, Dirk C, Montine, Thomas J, Kovacs, Gabor G, Lutz, Mirjam I, Fischer, Peter, Perrin, Richard J, Cairns, Nigel, Franklin, Erin E, Cohen, Herbert T, Sillero, Maria Inmaculada Cobos, Frost, Bess, Raj, Towfique, Goate, Alison, White, Charles L, and Crary, John F
Subjects: Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Genetics, Dementia, Alzheimer's Disease, Frontotemporal Dementia (FTD), Brain Disorders, Neurosciences, Biotechnology, Neurodegenerative, Aging, Acquired Cognitive Impairment, Aetiology, 2.1 Biological and endogenous factors, Neurological
Abstract: AbstractPrimary age-related tauopathy (PART) is a neurodegenerative tauopathy with features distinct from but also overlapping with Alzheimer disease (AD). While both exhibit Alzheimer-type temporal lobe neurofibrillary degeneration alongside amnestic cognitive impairment, PART develops independently of amyloid-β (Aβ) deposition in plaques. The pathogenesis of PART is unknown, but evidence suggests it is associated with genes that promote tau pathology as well as others that protect from Aβ toxicity. Here, we performed a genetic association study in an autopsy cohort of individuals with PART (n=647) using Braak neurofibrillary tangle stage as a quantitative trait adjusting for sex, age, genotyping platform, and principal components. We found significant associations with some candidate loci associated with AD and progressive supranuclear palsy, a primary tauopathy (SLC24A4, MS4A6A, HS3ST1, MAPT and EIF2AK3). Genome-wide association analysis revealed a novel significant association with a single nucleotide polymorphism on chromosome 4 (rs56405341) in a locus containing three genes, including JADE1 which was significantly upregulated in tangle-bearing neurons by single-soma RNA-seq. Immunohistochemical studies using antisera targeting JADE1 protein revealed localization within tau aggregates in autopsy brain from tauopathies containing isoforms with four microtubule-binding domain repeats (4R) and mixed 3R/4R, but not with 3R exclusively. Co-immunoprecipitation revealed a direct and specific binding of JADE1 protein to tau containing four (4R) and no N-terminal inserts (0N4R) in post-mortem human PART brain tissue. Finally, knockdown of the Drosophila JADE1 homolog rhinoceros (rno) enhanced tau-induced toxicity and apoptosis in vivo in a humanized 0N4R mutant tau knock-in model as quantified by rough eye phenotype and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) in the fly brain. Together, these findings indicate that PART has a genetic architecture that partially overlaps with AD and other tauopathies and suggests a novel role for JADE1 as a mediator of neurofibrillary degeneration.
Published: 2021

14. Early Selective Vulnerability of the CA2 Hippocampal Subfield in Primary Age-Related Tauopathy (vol 80, nlaa153, 2021)

Author: Walker, Jamie M, Richardson, Timothy E, Farrell, Kurt, Iida, Megan A, Foong, Chan, Shang, Ping, Attems, Johannes, Ayalon, Gai, Beach, Thomas G, Bigio, Eileen H, Budson, Andrew, Cairns, Nigel J, Corrada, Maria, Cortes, Etty, Dickson, Dennis W, Fischer, Peter, Flanagan, Margaret E, Franklin, Erin, Gearing, Marla, Glass, Jonathan, Hansen, Lawrence A, Haroutunian, Vahram, Hof, Patrick R, Honig, Lawrence, Kawas, Claudia, Keene, C Dirk, Kofler, Julia, Kovacs, Gabor G, Lee, Edward B, Lutz, Mirjam I, Mao, Qinwen, Masliah, Eliezer, McKee, Ann C, McMillan, Corey T, Mesulam, M Marsel, Murray, Melissa, Nelson, Peter T, Perrin, Richard, Pham, Thao, Poon, Wayne, Dushyant, P Purohit, Rissman, Robert A, Sakai, Kenji, Sano, Mary, Schneider, Julie A, Stein, Thor D, Teich, Andrew F, Trojanowski, John Q, Troncoso, Juan C, Vonsattel, Jean-Paul, Weintraub, Sandra, Wolk, David A, Woltjer, Randall L, Yamada, Masahito, Yu, Lei, White, Charles L, and Crary, John F
Subjects: Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Neurology & Neurosurgery, Clinical sciences
Published: 2021

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

Author: Reus, Lianne M, Pasaniuc, Bogdan, Posthuma, Danielle, Boltz, Toni, Consortium, International FTD-Genomics, Ferrari, Raffaele, Hernandez, Dena G, Nalls, Michael A, Rohrer, Jonathan D, Ramasamy, Adaikalavan, Kwok, John BJ, 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 RA, Hsiung, Ging-Yuek R, Mann, David MA, 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 CM, 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, and Gu, Wei
Subjects: Biological Sciences, Genetics, Frontotemporal Dementia (FTD), Neurodegenerative, Human Genome, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease Related Dementias (ADRD), Rare Diseases, Acquired Cognitive Impairment, Brain Disorders, Dementia, Aging, Biotechnology, Neurosciences, 2.1 Biological and endogenous factors, Neurological, Frontotemporal Dementia, Gene Expression, Humans, International FTD-Genomics Consortium, 17q21.31 inversion region, Dorsolateral prefrontal cortex, Expression quantitative trait loci, Frontotemporal dementia, SEC22B, Transcriptome-wide association study, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biological sciences, Biomedical and clinical sciences, Psychology
Abstract: BackgroundThe etiology of frontotemporal dementia (FTD) is poorly understood. To identify genes with predicted expression levels associated with FTD, we integrated summary statistics with external reference gene expression data using a transcriptome-wide association study approach.MethodsFUSION software was used to leverage FTD summary statistics (all FTD: n = 2154 cases, n = 4308 controls; behavioral variant FTD: n = 1337 cases, n = 2754 controls; semantic dementia: n = 308 cases, n = 616 controls; progressive nonfluent aphasia: n = 269 cases, n = 538 controls; FTD with motor neuron disease: n = 200 cases, n = 400 controls) from the International FTD-Genomics Consortium with 53 expression quantitative loci tissue type panels (n = 12,205; 5 consortia). Significance was assessed using a 5% false discovery rate threshold.ResultsWe identified 73 significant gene-tissue associations for FTD, representing 44 unique genes in 34 tissue types. Most significant findings were derived from dorsolateral prefrontal cortex splicing data (n = 19 genes, 26%). The 17q21.31 inversion locus contained 23 significant associations, representing 6 unique genes. Other top hits included SEC22B (a gene involved in vesicle trafficking), TRGV5, and ZNF302. A single gene finding (RAB38) was observed for behavioral variant FTD. For other clinical subtypes, no significant associations were observed.ConclusionsWe identified novel candidate genes (e.g., SEC22B) and previously reported risk regions (e.g., 17q21.31) for FTD. Most significant associations were observed in dorsolateral prefrontal cortex splicing data despite the modest sample size of this reference panel. This suggests that our findings are specific to FTD and are likely to be biologically relevant highlights of genes at different FTD risk loci that are contributing to the disease pathology.
Published: 2021

16. Neuropathological consensus criteria for the evaluation of Lewy pathology in post-mortem brains: a multi-centre study

Author: Attems, Johannes, Toledo, Jon B, Walker, Lauren, Gelpi, Ellen, Gentleman, Steve, Halliday, Glenda, Hortobagyi, Tibor, Jellinger, Kurt, Kovacs, Gabor G, Lee, Edward B, Love, Seth, McAleese, Kirsty E, Nelson, Peter T, Neumann, Manuela, Parkkinen, Laura, Polvikoski, Tuomo, Sikorska, Beata, Smith, Colin, Grinberg, Lea Tenenholz, Thal, Dietmar R, Trojanowski, John Q, and McKeith, Ian G
Subjects: Biomedical and Clinical Sciences, Neurosciences, Brain Disorders, Neurological, Autopsy, Brain, Brain Mapping, Consensus, Humans, Lewy Bodies, Lewy Body Disease, Observer Variation, Reproducibility of Results, Aging, Dementia, Acquired Cognitive Impairment, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Alzheimer's Disease, Parkinson's Disease, 2.1 Biological and endogenous factors, Aetiology, Aged, Aged, 80 and over, Alzheimer Disease, Cluster Analysis, Female, Male, Parkinson Disease, alpha-Synuclein, Lewy body disease, Diagnostic neuropathology, Clinical Sciences, Neurology & Neurosurgery
Abstract: Currently, the neuropathological diagnosis of Lewy body disease (LBD) may be stated according to several staging systems, which include the Braak Lewy body stages (Braak), the consensus criteria by McKeith and colleagues (McKeith), the modified McKeith system by Leverenz and colleagues (Leverenz), and the Unified Staging System by Beach and colleagues (Beach). All of these systems use semi-quantitative scoring (4- or 5-tier scales) of Lewy pathology (LP; i.e., Lewy bodies and Lewy neurites) in defined cortical and subcortical areas. While these systems are widely used, some suffer from low inter-rater reliability and/or an inability to unequivocally classify all cases with LP. To address these limitations, we devised a new system, the LP consensus criteria (LPC), which is based on the McKeith system, but applies a dichotomous approach for the scoring of LP (i.e., "absent" vs. "present") and includes amygdala-predominant and olfactory-only stages. α-Synuclein-stained slides from brainstem, limbic system, neocortex, and olfactory bulb from a total of 34 cases with LP provided by the Newcastle Brain Tissue Resource (NBTR) and the University of Pennsylvania brain bank (UPBB) were scanned and assessed by 16 raters, who provided diagnostic categories for each case according to Braak, McKeith, Leverenz, Beach, and LPC systems. In addition, using LP scores available from neuropathological reports of LP cases from UPBB (n = 202) and NBTR (n = 134), JT (UPBB) and JA (NBTR) assigned categories according to all staging systems to these cases. McKeith, Leverenz, and LPC systems reached good (Krippendorff's α ≈ 0.6), while both Braak and Beach systems had lower (Krippendorff's α ≈ 0.4) inter-rater reliability, respectively. Using the LPC system, all cases could be unequivocally classified by the majority of raters, which was also seen for 97.1% when the Beach system was used. However, a considerable proportion of cases could not be classified when using Leverenz (11.8%), McKeith (26.5%), or Braak (29.4%) systems. The category of neocortical LP according to the LPC system was associated with a 5.9 OR (p
Published: 2021

17. Genome-wide structural variant analysis identifies risk loci for non-Alzheimer’s dementias

Author: Soltis, Anthony R., Viollet, Coralie, Sukumar, Gauthaman, Alba, Camille, Lott, Nathaniel, McGrath Martinez, Elisa, Tuck, Meila, Singh, Jatinder, Bacikova, Dagmar, Zhang, Xijun, Hupalo, Daniel N., Adeleye, Adelani, Wilkerson, Matthew D., Pollard, Harvey B., Dalgard, Clifton L., Black, Sandra E., Gan-Or, Ziv, Keith, Julia, Masellis, Mario, Rogaeva, Ekaterina, Brice, Alexis, Lesage, Suzanne, Xiromerisiou, Georgia, Calvo, Andrea, Canosa, Antonio, Chio, Adriano, Logroscino, Giancarlo, Mora, Gabriele, Krüger, Reijko, May, Patrick, Alcolea, Daniel, Clarimon, Jordi, Fortea, Juan, Gonzalez-Aramburu, Isabel, Infante, Jon, Lage, Carmen, Lleó, Alberto, Pastor, Pau, Sanchez-Juan, Pascual, Brett, Francesca, Aarsland, Dag, Al-Sarraj, Safa, Attems, Johannes, Gentleman, Steve, Hardy, John A., Hodges, Angela K., Love, Seth, McKeith, Ian G., Morris, Christopher M., Morris, Huw R., Palmer, Laura, Pickering-Brown, Stuart, Ryten, Mina, Thomas, Alan J., Troakes, Claire, Albert, Marilyn S., Barrett, Matthew J., Beach, Thomas G., Bekris, Lynn M., Bennett, David A., Boeve, Bradley F., Dawson, Ted M., Dickson, Dennis W., Faber, Kelley, Ferman, Tanis, Ferrucci, Luigi, Flanagan, Margaret E., Foroud, Tatiana M., Ghetti, Bernardino, Gibbs, J. Raphael, Goate, Alison, Goldstein, David S., Graff-Radford, Neill R., Kaufmann, Horacio, Kukull, Walter A., Leverenz, James B., Lopez, Grisel, Mao, Qinwen, Masliah, Eliezer, Monuki, Edwin, Newell, Kathy L., Palma, Jose-Alberto, Perkins, Matthew, Pletnikova, Olga, Renton, Alan E., Resnick, Susan M., Rosenthal, Liana S., Ross, Owen A., Scherzer, Clemens R., Serrano, Geidy E., Shakkottai, Vikram G., Sidransky, Ellen, Tanaka, Toshiko, Tayebi, Nahid, Topol, Eric, Torkamani, Ali, Troncoso, Juan C., Woltjer, Randy, Wszolek, Zbigniew K., Scholz, Sonja W., Baloh, Robert H., Bowser, Robert, Broach, James, Camu, William, Chiò, Adriano, Cooper-Knock, John, Drepper, Carsten, Drory, Vivian E., Dunckley, Travis L., Feldman, Eva, Fratta, Pietro, Gerhard, Glenn, Gibson, Summer B., Glass, Jonathan D., Harms, Matthew B., Heiman-Patterson, Terry D., Jansson, Lilja, Kirby, Janine, Kwan, Justin, Laaksovirta, Hannu, Landers, John E., Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, MacGowan, Daniel J.L., Maragakis, Nicholas J., Mouzat, Kevin, Myllykangas, Liisa, Orrell, Richard W., Ostrow, Lyle W., Pamphlett, Roger, Pioro, Erik, Pulst, Stefan M., Ravits, John M., Robberecht, Wim, Rothstein, Jeffrey D., Sendtner, Michael, Shaw, Pamela J., Sidle, Katie C., Simmons, Zachary, Stein, Thor, Stone, David J., Tienari, Pentti J., Traynor, Bryan J., Valori, Miko, Van Damme, Philip, Van Deerlin, Vivianna M., Van Den Bosch, Ludo, Zinman, Lorne, Kaivola, Karri, Chia, Ruth, Ding, Jinhui, Rasheed, Memoona, Fujita, Masashi, Menon, Vilas, Walton, Ronald L., Collins, Ryan L., Billingsley, Kimberley, Brand, Harrison, Talkowski, Michael, Zhao, Xuefang, Dewan, Ramita, Stark, Ali, Ray, Anindita, Solaiman, Sultana, Alvarez Jerez, Pilar, Malik, Laksh, Tienari, Pentti, Mazzini, Letizia, D'Alfonso, Sandra, Moglia, Cristina, and De Jager, Philip L.
Published: 2023
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18. 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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19. Reply: LATE to the PART-y

Author: Nelson, Peter T, Dickson, Dennis W, Trojanowski, John Q, Jack, Clifford R, Boyle, Patricia A, Arfanakis, Konstantinos, Rademakers, Rosa, Alafuzoff, Irina, Attems, Johannes, Brayne, Carol, Coyle-Gilchrist, Ian TS, Fardo, David W, Flanagan, Margaret E, Halliday, Glenda, Hunter, Sally, Jicha, Gregory A, Katsumata, Yuriko, Kawas, Claudia H, Keene, C Dirk, Kovacs, Gabor G, Kukull, Walter A, Levey, Allan I, Makkinejad, Nazanin, Montine, Thomas J, Murray, Melissa E, Nag, Sukriti, Seeley, William W, Sperling, Reisa A, White, Charles L, and Schneider, Julie A
Subjects: Biomedical and Clinical Sciences, Health Sciences, Psychology, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences
Published: 2019

20. Erratum

Author: Nelson, Peter T, Dickson, Dennis W, Trojanowski, John Q, Jack, Clifford R Jr, Boyle, Patricia A, Arfanakis, Konstantinos, Rademakers, Rosa, Alafuzoff, Irina, Attems, Johannes, Brayne, Carol, Coyle-Gilchrist, Ian TS, Chui, Helena C, Fardo, David W, Flanagan, Margaret E, Halliday, Glenda, Hokkanen, Suvi RK, Hunter, Sally, Jicha, Gregory A, Katsumata, Yuriko, Kawas, Claudia H, Keene, C Dirk, Kovacs, Gabor G, Kukull, Walter A, Levey, Allan I, Makkinejad, Nazanin, Montine, Thomas J, Murayama, Shigeo, Murray, Melissa E, Nag, Sukriti, Rissman, Robert A, Seeley, William W, Sperling, Reisa A, White, Charles LIII, Yu, Lei, and Schneider, Julie A
Subjects: Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract: The publisher apologizes for erroneously omitting part of the footnote for Table 2. This has now been corrected both online and in print.
Published: 2019

21. Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report.

Author: Nelson, Peter T, Dickson, Dennis W, Trojanowski, John Q, Jack, Clifford R, Boyle, Patricia A, Arfanakis, Konstantinos, Rademakers, Rosa, Alafuzoff, Irina, Attems, Johannes, Brayne, Carol, Coyle-Gilchrist, Ian TS, Chui, Helena C, Fardo, David W, Flanagan, Margaret E, Halliday, Glenda, Hokkanen, Suvi RK, Hunter, Sally, Jicha, Gregory A, Katsumata, Yuriko, Kawas, Claudia H, Keene, C Dirk, Kovacs, Gabor G, Kukull, Walter A, Levey, Allan I, Makkinejad, Nazanin, Montine, Thomas J, Murayama, Shigeo, Murray, Melissa E, Nag, Sukriti, Rissman, Robert A, Seeley, William W, Sperling, Reisa A, White Iii, Charles L, Yu, Lei, and Schneider, Julie A
Subjects: Brain, Humans, Brain Diseases, Alzheimer Disease, Retrospective Studies, Aged, Aged, 80 and over, Middle Aged, Female, Male, Frontotemporal Lobar Degeneration, TDP-43 Proteinopathies, Frontotemporal Dementia, Neuroimaging, FTLD, MRI, PET, SNAP, epidemiology, and over, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract: We describe a recently recognized disease entity, limbic-predominant age-related TDP-43 encephalopathy (LATE). LATE neuropathological change (LATE-NC) is defined by a stereotypical TDP-43 proteinopathy in older adults, with or without coexisting hippocampal sclerosis pathology. LATE-NC is a common TDP-43 proteinopathy, associated with an amnestic dementia syndrome that mimicked Alzheimer's-type dementia in retrospective autopsy studies. LATE is distinguished from frontotemporal lobar degeneration with TDP-43 pathology based on its epidemiology (LATE generally affects older subjects), and relatively restricted neuroanatomical distribution of TDP-43 proteinopathy. In community-based autopsy cohorts, ∼25% of brains had sufficient burden of LATE-NC to be associated with discernible cognitive impairment. Many subjects with LATE-NC have comorbid brain pathologies, often including amyloid-β plaques and tauopathy. Given that the 'oldest-old' are at greatest risk for LATE-NC, and subjects of advanced age constitute a rapidly growing demographic group in many countries, LATE has an expanding but under-recognized impact on public health. For these reasons, a working group was convened to develop diagnostic criteria for LATE, aiming both to stimulate research and to promote awareness of this pathway to dementia. We report consensus-based recommendations including guidelines for diagnosis and staging of LATE-NC. For routine autopsy workup of LATE-NC, an anatomically-based preliminary staging scheme is proposed with TDP-43 immunohistochemistry on tissue from three brain areas, reflecting a hierarchical pattern of brain involvement: amygdala, hippocampus, and middle frontal gyrus. LATE-NC appears to affect the medial temporal lobe structures preferentially, but other areas also are impacted. Neuroimaging studies demonstrated that subjects with LATE-NC also had atrophy in the medial temporal lobes, frontal cortex, and other brain regions. Genetic studies have thus far indicated five genes with risk alleles for LATE-NC: GRN, TMEM106B, ABCC9, KCNMB2, and APOE. The discovery of these genetic risk variants indicate that LATE shares pathogenetic mechanisms with both frontotemporal lobar degeneration and Alzheimer's disease, but also suggests disease-specific underlying mechanisms. Large gaps remain in our understanding of LATE. For advances in prevention, diagnosis, and treatment, there is an urgent need for research focused on LATE, including in vitro and animal models. An obstacle to clinical progress is lack of diagnostic tools, such as biofluid or neuroimaging biomarkers, for ante-mortem detection of LATE. Development of a disease biomarker would augment observational studies seeking to further define the risk factors, natural history, and clinical features of LATE, as well as eventual subject recruitment for targeted therapies in clinical trials.
Published: 2019

22. Extravascular fibrinogen in the white matter of Alzheimer’s disease and normal aged brains: implications for fibrinogen as a biomarker for Alzheimer’s disease

Author: McAleese, Kirsty E, Graham, Sophie, Dey, Madhurima, Walker, Lauren, Erskine, Daniel, Johnson, Mary, Johnston, Eleanor, Thomas, Alan J, McKeith, Ian G, DeCarli, Charles, and Attems, Johannes
Subjects: Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Brain Disorders, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Alzheimer's Disease, Acquired Cognitive Impairment, Dementia, Aetiology, 2.1 Biological and endogenous factors, Neurological, Aged, Aged, 80 and over, Alzheimer Disease, Arteriolosclerosis, Biomarkers, Blood-Brain Barrier, Brain, Cerebral Amyloid Angiopathy, Cerebral Small Vessel Diseases, Female, Fibrinogen, Humans, Leukoencephalopathies, Male, Middle Aged, Plaque, Amyloid, White Matter, tau Proteins, Alzheimer's disease, biomarker, blood-brain barrier, cerebral small vessel disease, fibrinogen, white matter hyperintensities, white matter lesion, Alzheimer’s disease, Neurology & Neurosurgery, Clinical sciences
Abstract: The blood-brain barrier (BBB) regulates cerebrovascular permeability and leakage of blood-derived fibrinogen. Dysfunction of the BBB has been associated with cerebral arteriolosclerosis small vessel disease (SVD) and white matter lesions (WML). Furthermore, BBB dysfunction is associated with the pathogenesis of Alzheimer's disease (AD) with the presence of CSF plasma proteins suggested to be a potential biomarker of AD. We aimed to determine if extravascular fibrinogen in the white matter was associated with the development of AD hallmark pathologies, i.e., hyperphosphorylated tau (HPτ) and amyloid-β (Aβ), as well as SVD, cerebral amyloid angiopathy (CAA) and measures of white matter damage. Using human post-mortem brains, parietal tissue from 20 AD and 22 non-demented controls was quantitatively assessed for HPτ, Aβ, white matter damage severity, axonal density, demyelination and the burden of extravascular fibrinogen in both WML and normal appearing white matter (NAWM). SVD severity was determined by calculating sclerotic indices. WML- and NAWM fibrinogen burden was not significantly different between AD and controls nor was it associated with the burden of HPτ or Aβ pathology, or any measures of white matter damage. Increasing severity of SVD was associated with and a predictor of both higher WML- and NAWM fibrinogen burden (all P
Published: 2019

23. Interpretable deep learning of myelin histopathology in age-related cognitive impairment

Author: McKenzie, Andrew T., Marx, Gabriel A., Koenigsberg, Daniel, Sawyer, Mary, Iida, Megan A., Walker, Jamie M., Richardson, Timothy E., Campanella, Gabriele, Attems, Johannes, McKee, Ann C., Stein, Thor D., Fuchs, Thomas J., White, III, Charles L., Farrell, Kurt, and Crary, John F.
Published: 2022
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24. Nuclear alpha-synuclein is present in the human brain and is modified in dementia with Lewy bodies

Author: Koss, David J., Erskine, Daniel, Porter, Andrew, Palmoski, Pawel, Menon, Hariharan, Todd, Olivia G. J., Leite, Marta, Attems, Johannes, and Outeiro, Tiago F.
Published: 2022
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25. Mitochondrial dysfunction is a key pathological driver of early stage Parkinson’s

Author: Toomey, Christina E., Heywood, Wendy E., Evans, James R., Lachica, Joanne, Pressey, Sarah N., Foti, Sandrine C., Al Shahrani, Mesfer, D’Sa, Karishma, Hargreaves, Iain P., Heales, Simon, Orford, Michael, Troakes, Claire, Attems, Johannes, Gelpi, Ellen, Palkovits, Miklos, Lashley, Tammaryn, Gentleman, Steve M., Revesz, Tamas, Mills, Kevin, and Gandhi, Sonia
Published: 2022
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26. MAPT H2 haplotype and risk of Pick's disease in the Pick's disease International Consortium: a genetic association study

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, Christopher, Elizabeth A, additional, DeTure, Michael, additional, Seeley, William W, additional, Lee, Edward B, additional, Frosch, Matthew P, additional, Molina-Porcel, Laura, additional, Gefen, Tamar, additional, Redding-Ochoa, Javier, additional, Ghetti, Bernardino, additional, Robinson, Andrew C, additional, Kobylecki, Christopher, additional, Rowe, James B, additional, Beach, Thomas G, additional, Teich, Andrew F, additional, Keith, Julia L, additional, Bodi, Istvan, additional, Halliday, Glenda M, additional, Gearing, Marla, additional, Arzberger, Thomas, additional, Morris, Christopher M, additional, White, Charles L, additional, Mechawar, Naguib, additional, Boluda, Susana, additional, MacKenzie, Ian R, additional, McLean, Catriona, additional, Cykowski, Matthew D, additional, Wang, Shih-Hsiu J, additional, Graff, Caroline, additional, Nagra, Rashed M, additional, Kovacs, Gabor G, additional, Giaccone, Giorgio, additional, Neumann, Manuela, additional, Ang, Lee-Cyn, additional, Carvalho, Agostinho, additional, Morris, Huw R, additional, Rademakers, Rosa, additional, Hardy, John A, additional, Dickson, Dennis W, additional, Rohrer, Jonathan D, additional, Ross, Owen A, additional, Warner, Thomas T, additional, Jaunmuktane, Zane, additional, Boeve, Bradley F, 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, Petersen, Ronald C, additional, Whitwell, Jennifer L, additional, Grinberg, Lea T, additional, Miller, Bruce, additional, Schlereth, Athena, additional, Spina, Salvatore, additional, Grossman, Murray, additional, Irwin, David J, 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, Oakley, Derek H, additional, Aldecoa, Iban, additional, Balasa, Mircea, additional, Gelpi, Ellen, additional, Borrego-Écija, Sergi, additional, Gascon-Bayarri, Jordi, additional, Sánchez-Valle, Raquel, additional, Sanz-Cartagena, Pilar, additional, Piñol-Ripoll, Gerard, additional, Bigio, Eileen H, additional, Flanagan, Margaret E, additional, Rogalski, Emily J, additional, Weintraub, Sandra, additional, Schneider, Julie A, additional, Peng, Lihua, additional, Zhu, Xiongwei, additional, Chang, Koping, additional, Troncoso, Juan C, additional, Prokop, Stefan, additional, Newell, Kathy L, additional, Jones, Matthew, additional, Richardson, Anna, additional, Roncaroli, Federico, additional, Snowden, Julie, additional, Allinson, Kieren, additional, Singh, Poonam, additional, Serrano, Geidy E, additional, Flowers, Xena E, additional, Goldman, James E, additional, Heaps, Allison C, additional, Leskinen, Sandra P, additional, Black, Sandra E, additional, Masellis, Mario, additional, King, Andrew, additional, Al-Sarraj, Safa, additional, Troakes, Claire, additional, Hodges, John R, additional, Kril, Jillian J, additional, Kwok, John B, additional, Piguet, Olivier, additional, Roeber, Sigrun, additional, Attems, Johannes, additional, Thomas, Alan J, additional, Evers, Bret M., additional, Bieniek, Kevin F, additional, Sieben, Anne A, additional, Cras, Patrick P, additional, De Vil, Bart B, additional, Bird, Thomas, additional, Castellani, Rudolph J, additional, Chaffee, Ann, additional, Franklin, Erin, additional, Haroutunian, Vahram, additional, Jacobsen, Max, additional, Keene, Dirk, additional, Latimer, Caitlin S, additional, Metcalf, Jeff, additional, Perrin, Richard J, additional, Purohit, Dushyant P, additional, Rissman, Robert A, additional, Schantz, Aimee, additional, Walker, Jamie, additional, De Deyn, Peter P, additional, Duyckaerts, Charles, additional, Le Ber, Isabelle, additional, Seilhean, Danielle, additional, Turbant-Leclere, Sabrina, additional, Ervin, John F, additional, Nennesmo, Inger, additional, Riehl, James, additional, Nacmias, Benedetta, additional, Finger, Elizabeth C, additional, Blauwendraat, Cornelis, additional, Nalls, Mike A, additional, Singleton, Andrew B, additional, Vitale, Dan, additional, Cunha, Cristina, additional, and Wszolek, Zbigniew K, additional
Published: 2024
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27. Insights into Lewy body disease from rare neurometabolic disorders

Author: Erskine, Daniel and Attems, Johannes
Published: 2021
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28. 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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29. Diagnosis and management of dementia with Lewy bodies

Author: McKeith, Ian G, Boeve, Bradley F, Dickson, Dennis W, Halliday, Glenda, Taylor, John-Paul, Weintraub, Daniel, Aarsland, Dag, Galvin, James, Attems, Johannes, Ballard, Clive G, Bayston, Ashley, Beach, Thomas G, Blanc, Frédéric, Bohnen, Nicolaas, Bonanni, Laura, Bras, Jose, Brundin, Patrik, Burn, David, Chen-Plotkin, Alice, Duda, John E, El-Agnaf, Omar, Feldman, Howard, Ferman, Tanis J, Ffytche, Dominic, Fujishiro, Hiroshige, Galasko, Douglas, Goldman, Jennifer G, Gomperts, Stephen N, Graff-Radford, Neill R, Honig, Lawrence S, Iranzo, Alex, Kantarci, Kejal, Kaufer, Daniel, Kukull, Walter, Lee, Virginia MY, Leverenz, James B, Lewis, Simon, Lippa, Carol, Lunde, Angela, Masellis, Mario, Masliah, Eliezer, McLean, Pamela, Mollenhauer, Brit, Montine, Thomas J, Moreno, Emilio, Mori, Etsuro, Murray, Melissa, O'Brien, John T, Orimo, Sotoshi, Postuma, Ronald B, Ramaswamy, Shankar, Ross, Owen A, Salmon, David P, Singleton, Andrew, Taylor, Angela, Thomas, Alan, Tiraboschi, Pietro, Toledo, Jon B, Trojanowski, John Q, Tsuang, Debby, Walker, Zuzana, Yamada, Masahito, and Kosaka, Kenji
Subjects: Brain Disorders, Clinical Research, Acquired Cognitive Impairment, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease Related Dementias (ADRD), Lewy Body Dementia, Alzheimer's Disease, Prevention, Aging, Dementia, Neurodegenerative, Neurological, Biomarkers, Humans, Lewy Body Disease, Practice Guidelines as Topic, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract: The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade. The revised DLB consensus criteria now distinguish clearly between clinical features and diagnostic biomarkers, and give guidance about optimal methods to establish and interpret these. Substantial new information has been incorporated about previously reported aspects of DLB, with increased diagnostic weighting given to REM sleep behavior disorder and 123iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. The diagnostic role of other neuroimaging, electrophysiologic, and laboratory investigations is also described. Minor modifications to pathologic methods and criteria are recommended to take account of Alzheimer disease neuropathologic change, to add previously omitted Lewy-related pathology categories, and to include assessments for substantia nigra neuronal loss. Recommendations about clinical management are largely based upon expert opinion since randomized controlled trials in DLB are few. Substantial progress has been made since the previous report in the detection and recognition of DLB as a common and important clinical disorder. During that period it has been incorporated into DSM-5, as major neurocognitive disorder with Lewy bodies. There remains a pressing need to understand the underlying neurobiology and pathophysiology of DLB, to develop and deliver clinical trials with both symptomatic and disease-modifying agents, and to help patients and carers worldwide to inform themselves about the disease, its prognosis, best available treatments, ongoing research, and how to get adequate support.
Published: 2017

30. Multisite Assessment of Aging-Related Tau Astrogliopathy (ARTAG).

Author: Kovacs, Gabor G, Xie, Sharon X, Lee, Edward B, Robinson, John L, Caswell, Carrie, Irwin, David J, Toledo, Jon B, Johnson, Victoria E, Smith, Douglas H, Alafuzoff, Irina, Attems, Johannes, Bencze, Janos, Bieniek, Kevin F, Bigio, Eileen H, Bodi, Istvan, Budka, Herbert, Dickson, Dennis W, Dugger, Brittany N, Duyckaerts, Charles, Ferrer, Isidro, Forrest, Shelley L, Gelpi, Ellen, Gentleman, Stephen M, Giaccone, Giorgio, Grinberg, Lea T, Halliday, Glenda M, Hatanpaa, Kimmo J, Hof, Patrick R, Hofer, Monika, Hortobágyi, Tibor, Ironside, James W, King, Andrew, Kofler, Julia, Kövari, Enikö, Kril, Jillian J, Love, Seth, Mackenzie, Ian R, Mao, Qinwen, Matej, Radoslav, McLean, Catriona, Munoz, David G, Murray, Melissa E, Neltner, Janna, Nelson, Peter T, Ritchie, Diane, Rodriguez, Roberta D, Rohan, Zdenek, Rozemuller, Annemieke, Sakai, Kenji, Schultz, Christian, Seilhean, Danielle, Smith, Vanessa, Tacik, Pawel, Takahashi, Hitoshi, Takao, Masaki, Rudolf Thal, Dietmar, Weis, Serge, Wharton, Stephen B, White, Charles L, Woulfe, John M, Yamada, Masahito, and Trojanowski, John Q
Subjects: Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Frontotemporal Dementia (FTD), Aging, Neurodegenerative, Acquired Cognitive Impairment, Brain Disorders, Alzheimer's Disease, Aged, Aged, 80 and over, Astrocytes, Female, Humans, Male, Middle Aged, Severity of Illness Index, Tauopathies, tau Proteins, ARTAG, Digital pathology, Interrater agreement, Neuropathology, Tau, Tau-astrogliopathy, Clinical Sciences, Neurosciences, Neurology & Neurosurgery
Abstract: Aging-related tau astrogliopathy (ARTAG) is a recently introduced terminology. To facilitate the consistent identification of ARTAG and to distinguish it from astroglial tau pathologies observed in the primary frontotemporal lobar degeneration tauopathies we evaluated how consistently neuropathologists recognize (1) different astroglial tau immunoreactivities, including those of ARTAG and those associated with primary tauopathies (Study 1); (2) ARTAG types (Study 2A); and (3) ARTAG severity (Study 2B). Microphotographs and scanned sections immunostained for phosphorylated tau (AT8) were made available for download and preview. Percentage of agreement and kappa values with 95% confidence interval (CI) were calculated for each evaluation. The overall agreement for Study 1 was >60% with a kappa value of 0.55 (95% CI 0.433-0.645). Moderate agreement (>90%, kappa 0.48, 95% CI 0.457-0.900) was reached in Study 2A for the identification of ARTAG pathology for each ARTAG subtype (kappa 0.37-0.72), whereas fair agreement (kappa 0.40, 95% CI 0.341-0.445) was reached for the evaluation of ARTAG severity. The overall assessment of ARTAG showed moderate agreement (kappa 0.60, 95% CI 0.534-0.653) among raters. Our study supports the application of the current harmonized evaluation strategy for ARTAG with a slight modification of the evaluation of its severity.
Published: 2017

31. Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis

Author: Adeleye, Adelani, Alba, Camille, Bacikova, Dagmar, Hupalo, Daniel N., Martinez, Elisa McGrath, Pollard, Harvey B., Sukumar, Gauthaman, Soltis, Anthony R., Tuck, Meila, Zhang, Xijun, Wilkerson, Matthew D., Smith, Bradley N., Ticozzi, Nicola, Fallini, Claudia, Gkazi, Athina Soragia, Topp, Simon D., Kost, Jason, Scotter, Emma L., Kenna, Kevin P., Miller, Jack W., Tiloca, Cinzia, Vance, Caroline, Danielson, Eric W., Troakes, Claire, Colombrita, Claudia, Al-Sarraj, Safa, Lewis, Elizabeth A., King, Andrew, Calini, Daniela, Pensato, Viviana, Castellotti, Barbara, de Belleroche, Jacqueline, Baas, Frank, ten Asbroek, Anneloor L.M.A., Sapp, Peter C., McKenna-Yasek, Diane, McLaughlin, Russell L., Polak, Meraida, Asress, Seneshaw, Esteban-Pérez, Jesús, Muñoz-Blanco, José Luis, Stevic, Zorica, D’Alfonso, Sandra, Mazzini, Letizia, Comi, Giacomo P., Del Bo, Roberto, Ceroni, Mauro, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, van Rheenen, Wouter, Diekstra, Frank P., Rademakers, Rosa, van Blitterswijk, Marka, Boylan, Kevin B., Lauria, Giuseppe, Duga, Stefano, Corti, Stefania, Cereda, Cristina, Corrado, Lucia, Sorarù, Gianni, Williams, Kelly L., Nicholson, Garth A., Blair, Ian P., Leblond-Manry, Claire, Rouleau, Guy A., Hardiman, Orla, Morrison, Karen E., Veldink, Jan H., van den Berg, Leonard H., Al-Chalabi, Ammar, Pall, Hardev, Shaw, Pamela J., Turner, Martin R., Talbot, Kevin, Taroni, Franco, García-Redondo, Alberto, Wu, Zheyang, Gellera, Cinzia, Ratti, Antonia, Brown, Robert H., Jr., Shaw, Christopher E., Ambrose, John C., Arumugam, Prabhu, Baple, Emma L., Bleda, Marta, Boardman-Pretty, Freya, Boissiere, Jeanne M., Boustred, Christopher R., Brittain, H., Caulfield, Mark J., Chan, Georgia C., Craig, Clare E.H., Daugherty, Louise C., de Burca, Anna, Devereau, Andrew, Elgar, Greg, Foulger, Rebecca E., Fowler, Tom, Furió-Tarí, Pedro, Hackett, Joanne M., Halai, Dina, Hamblin, Angela, Henderson, Shirley, Holman, James E., Hubbard, Tim J.P., Jackson, Rob, Jones, Louise J., Kasperaviciute, Dalia, Kayikci, Melis, Lahnstein, Lea, Lawson, Kay, Leigh, Sarah E.A., Leong, Ivonne U.S., Lopez, Javier F., Maleady-Crowe, Fiona, Mason, Joanne, McDonagh, Ellen M., Moutsianas, Loukas, Mueller, Michael, Murugaesu, Nirupa, Need, Anna C., Odhams, Chris A., Patch, Christine, Perez-Gil, Daniel, Polychronopoulos, Dimitris, Pullinger, John, Rahim, Tahrima, Rendon, Augusto, Riesgo-Ferreiro, Pablo, Rogers, Tim, Savage, Kevin, Sawant, Kushmita, Scott, Richard H., Siddiq, Afshan, Sieghart, Alexander, Smedley, Damian, Smith, Katherine R., Sosinsky, Alona, Spooner, William, Stevens, Helen E., Stuckey, Alexander, Sultana, Razvan, Thomas, Ellen R.A., Thompson, Simon R., Tregidgo, Carolyn, Walsh, Emma, Watters, Sarah A., Welland, Matthew J., Williams, Eleanor, Witkowska, Katarzyna, Wood, Suzanne M., Zarowiecki, Magdalena, Arepalli, Sampath, Auluck, Pavan, Baloh, Robert H., Bowser, Robert, Brice, Alexis, Broach, James, Camu, William, Chiò, Adriano, Cooper-Knock, John, Corcia, Philippe, Drepper, Carsten, Drory, Vivian E., Dunckley, Travis L., Faghri, Faraz, Farren, Jennifer, Feldman, Eva, Floeter, Mary Kay, Fratta, Pietro, Gerhard, Glenn, Gibson, Summer B., Goutman, Stephen A., Heiman-Patterson, Terry D., Hernandez, Dena G., Hoover, Ben, Jansson, Lilja, Kamel, Freya, Kirby, Janine, Kowall, Neil W., Laaksovirta, Hannu, Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, MacGowan, Daniel JL., Maragakis, Nicholas J., Mora, Gabriele, Mouzat, Kevin, Myllykangas, Liisa, Nalls, Mike A., Orrell, Richard W., Ostrow, Lyle W., Pamphlett, Roger, Pioro, Erik, Pulst, Stefan M., Ravits, John M., Renton, Alan E., Robberecht, Wim, Robey, Ian, Rogaeva, Ekaterina, Rothstein, Jeffrey D., Sendtner, Michael, Sidle, Katie C., Simmons, Zachary, Stone, David J., Tienari, Pentti J., Trojanowski, John Q., Troncoso, Juan C., Valori, Miko, Van Damme, Philip, Van Den Bosch, Ludo, Zinman, Lorne, Albani, Diego, Borroni, Barbara, Padovani, Alessandro, Bruni, Amalia, Clarimon, Jordi, Dols-Icardo, Oriol, Illán-Gala, Ignacio, Lleó, Alberto, Danek, Adrian, Galimberti, Daniela, Scarpini, Elio, Serpente, Maria, Graff, Caroline, Chiang, Huei-Hsin, Khoshnood, Behzad, Öijerstedt, Linn, Morris, Christopher M., Nacmias, Benedetta, Sorbi, Sandro, Nielsen, Jorgen E., Hjermind, Lynne E., Novelli, Valeria, Puca, Annibale A., Pastor, Pau, Alvarez, Ignacio, Diez-Fairen, Monica, Aguilar, Miquel, Perneczky, Robert, Diehl-Schimd, Janine, Rossi, Mina, Ruiz, Agustin, Boada, Mercè, Hernández, Isabel, Moreno-Grau, Sonia, Schlachetzki, Johannes C., Aarsland, Dag, Albert, Marilyn S., Attems, Johannes, Barrett, Matthew J., Beach, Thomas G., Bekris, Lynn M., Bennett, David A., Besser, Lilah M., Bigio, Eileen H., Black, Sandra E., Boeve, Bradley F., Bohannan, Ryan C., Brett, Francesca, Brunetti, Maura, Caraway, Chad A., Palma, Jose-Alberto, Calvo, Andrea, Canosa, Antonio, Dickson, Dennis, Duyckaerts, Charles, Faber, Kelley, Ferman, Tanis, Flanagan, Margaret E., Floris, Gianluca, Foroud, Tatiana M., Fortea, Juan, Gan-Or, Ziv, Gentleman, Steve, Ghetti, Bernardino, Gibbs, Jesse Raphael, Goate, Alison, Goldstein, David, González-Aramburu, Isabel, Graff-Radford, Neill R., Hodges, Angela K., Hu, Heng-Chen, Hupalo, Daniel, Infante, Jon, Iranzo, Alex, Kaiser, Scott M., Kaufmann, Horacio, Keith, Julia, Kim, Ronald C., Klein, Gregory, Krüger, Rejko, Kukull, Walter, Kuzma, Amanda, Lage, Carmen, Lesage, Suzanne, Leverenz, James B., Logroscino, Giancarlo, Lopez, Grisel, Love, Seth, Mao, Qinwen, Marti, Maria Jose, Martinez-McGrath, Elisa, Masellis, Mario, Masliah, Eliezer, May, Patrick, McKeith, Ian, Mesulam, Marek-Marsel, Monuki, Edwin S., Newell, Kathy L., Norcliffe-Kaufmann, Lucy, Palmer, Laura, Perkins, Matthew, Pletnikova, Olga, Molina-Porcel, Laura, Reynolds, Regina H., Rodríguez-Rodríguez, Eloy, Rohrer, Jonathan D., Sanchez-Juan, Pascual, Scherzer, Clemens R., Serrano, Geidy E., Shakkottai, Vikram, Sidransky, Ellen, Tayebi, Nahid, Thomas, Alan J., Tilley, Bension S., Walton, Ronald L., Woltjer, Randy, Wszolek, Zbigniew K., Xiromerisiou, Georgia, Zecca, Chiara, Phatnani, Hemali, Kwan, Justin, Sareen, Dhruv, Broach, James R., Arcila-Londono, Ximena, Lee, Edward B., Shneider, Neil A., Fraenkel, Ernest, Zaitlen, Noah, Berry, James D., Malaspina, Andrea, Cox, Gregory A., Thompson, Leslie M., Finkbeiner, Steve, Dardiotis, Efthimios, Miller, Timothy M., Chandran, Siddharthan, Pal, Suvankar, Hornstein, Eran, MacGowan, Daniel J., Heiman-Patterson, Terry, Hammell, Molly G., Patsopoulos, Nikolaos.A., Butovsky, Oleg, Dubnau, Joshua, Nath, Avindra, Harms, Matt, Aronica, Eleonora, Poss, Mary, Phillips-Cremins, Jennifer, Crary, John, Atassi, Nazem, Lange, Dale J., Adams, Darius J., Stefanis, Leonidas, Gotkine, Marc, Babu, Suma, Raj, Towfique, Paganoni, Sabrina, Shalem, Ophir, Smith, Colin, Zhang, Bin, Harris, Brent, Broce, Iris, Drory, Vivian, Ravits, John, McMillan, Corey, Menon, Vilas, Wu, Lani, Altschuler, Steven, Amar, Khaled, Archibald, Neil, Bandmann, Oliver, Capps, Erica, Church, Alistair, Coebergh, Jan, Costantini, Alyssa, Critchley, Peter, Ghosh, Boyd CP., Hu, Michele T.M., Kobylecki, Christopher, Leigh, P. Nigel, Mann, Carl, Massey, Luke A., Morris, Huw R., Nath, Uma, Pavese, Nicola, Paviour, Dominic, Sharma, Jagdish, Vaughan, Jenny, Dewan, Ramita, Chia, Ruth, Ding, Jinhui, Hickman, Richard A., Stein, Thor D., Abramzon, Yevgeniya, Ahmed, Sarah, Sabir, Marya S., Portley, Makayla K., Tucci, Arianna, Ibáñez, Kristina, Shankaracharya, F.N.U., Keagle, Pamela, Rossi, Giacomina, Caroppo, Paola, Tagliavini, Fabrizio, Waldo, Maria L., Johansson, Per M., Nilsson, Christer F., Rowe, James B., Benussi, Luisa, Binetti, Giuliano, Ghidoni, Roberta, Jabbari, Edwin, Viollet, Coralie, Glass, Jonathan D., Singleton, Andrew B., Silani, Vincenzo, Ross, Owen A., Ryten, Mina, Torkamani, Ali, Tanaka, Toshiko, Ferrucci, Luigi, Resnick, Susan M., Pickering-Brown, Stuart, Brady, Christopher B., Kowal, Neil, Hardy, John A., Van Deerlin, Vivianna, Vonsattel, Jean Paul, Harms, Matthew B., Ferrari, Raffaele, Landers, John E., Gibbs, J. Raphael, Dalgard, Clifton L., Scholz, Sonja W., and Traynor, Bryan J.
Published: 2021
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32. Discovery of autism/intellectual disability somatic mutations in Alzheimer's brains: mutated ADNP cytoskeletal impairments and repair as a case study

Author: Ivashko-Pachima, Yanina, Hadar, Adva, Grigg, Iris, Korenková, Vlasta, Kapitansky, Oxana, Karmon, Gidon, Gershovits, Michael, Sayas, C. Laura, Kooy, R. Frank, Attems, Johannes, Gurwitz, David, and Gozes, Illana
Published: 2021
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33. Lipids, lysosomes and mitochondria: insights into Lewy body formation from rare monogenic disorders

Author: Erskine, Daniel, Koss, David, Korolchuk, Viktor I., Outeiro, Tiago F., Attems, Johannes, and McKeith, Ian
Published: 2021
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34. Neurodegenerative Diseases and Ageing

Author: Walker, Lauren, McAleese, Kirsty E., Erskine, Daniel, Attems, Johannes, Harris, J. Robin, Series Editor, and Korolchuk, Viktor I., editor
Published: 2019
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35. Relationship Between Tau, β Amyloid and α-Synuclein Pathologies

Author: Walker, Lauren, Attems, Johannes, Crusio, Wim E., Series Editor, Lambris, John D., Series Editor, Radeke, Heinfried H., Series Editor, Rezaei, Nima, Series Editor, Takashima, Akihiko, editor, Wolozin, Benjamin, editor, and Buee, Luc, editor
Published: 2019
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36. The Leukotriene Receptor Antagonist Montelukast Reduces Alpha-Synuclein Load and Restores Memory in an Animal Model of Dementia with Lewy Bodies

Author: Marschallinger, Julia, Altendorfer, Barbara, Rockenstein, Edward, Holztrattner, Miriam, Garnweidner-Raith, Julia, Pillichshammer, Nadine, Leister, Iris, Hutter-Paier, Birgit, Strempfl, Katharina, Unger, Michael S., Chishty, Mansoor, Felder, Thomas, Johnson, Mary, Attems, Johannes, Masliah, Eliezer, and Aigner, Ludwig
Published: 2020
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37. Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture

Author: Chia, Ruth, Sabir, Marya S., Bandres-Ciga, Sara, Saez-Atienzar, Sara, Reynolds, Regina H., Gustavsson, Emil, Walton, Ronald L., Ahmed, Sarah, Viollet, Coralie, Ding, Jinhui, Makarious, Mary B., Diez-Fairen, Monica, Portley, Makayla K., Shah, Zalak, Abramzon, Yevgeniya, Hernandez, Dena G., Blauwendraat, Cornelis, Stone, David J., Eicher, John, Parkkinen, Laura, Ansorge, Olaf, Clark, Lorraine, Honig, Lawrence S., Marder, Karen, Lemstra, Afina, St George-Hyslop, Peter, Londos, Elisabet, Morgan, Kevin, Lashley, Tammaryn, Warner, Thomas T., Jaunmuktane, Zane, Galasko, Douglas, Santana, Isabel, Tienari, Pentti J., Myllykangas, Liisa, Oinas, Minna, Cairns, Nigel J., Morris, John C., Halliday, Glenda M., Van Deerlin, Vivianna M., Trojanowski, John Q., Grassano, Maurizio, Calvo, Andrea, Mora, Gabriele, Canosa, Antonio, Floris, Gianluca, Bohannan, Ryan C., Brett, Francesca, Gan-Or, Ziv, Geiger, Joshua T., Moore, Anni, May, Patrick, Krüger, Rejko, Goldstein, David S., Lopez, Grisel, Tayebi, Nahid, Sidransky, Ellen, Norcliffe-Kaufmann, Lucy, Palma, Jose-Alberto, Kaufmann, Horacio, Shakkottai, Vikram G., Perkins, Matthew, Newell, Kathy L., Gasser, Thomas, Schulte, Claudia, Landi, Francesco, Salvi, Erika, Cusi, Daniele, Masliah, Eliezer, Kim, Ronald C., Caraway, Chad A., Monuki, Edwin S., Brunetti, Maura, Dawson, Ted M., Rosenthal, Liana S., Albert, Marilyn S., Pletnikova, Olga, Troncoso, Juan C., Flanagan, Margaret E., Mao, Qinwen, Bigio, Eileen H., Rodríguez-Rodríguez, Eloy, Infante, Jon, Lage, Carmen, González-Aramburu, Isabel, Sanchez-Juan, Pascual, Ghetti, Bernardino, Keith, Julia, Black, Sandra E., Masellis, Mario, Rogaeva, Ekaterina, Duyckaerts, Charles, Brice, Alexis, Lesage, Suzanne, Xiromerisiou, Georgia, Barrett, Matthew J., Tilley, Bension S., Gentleman, Steve, Logroscino, Giancarlo, Serrano, Geidy E., Beach, Thomas G., McKeith, Ian G., Thomas, Alan J., Attems, Johannes, Morris, Christopher M., Palmer, Laura, Love, Seth, Troakes, Claire, Al-Sarraj, Safa, Hodges, Angela K., Aarsland, Dag, Klein, Gregory, Kaiser, Scott M., Woltjer, Randy, Pastor, Pau, Bekris, Lynn M., Leverenz, James B., Besser, Lilah M., Kuzma, Amanda, Renton, Alan E., Goate, Alison, Bennett, David A., Scherzer, Clemens R., Morris, Huw R., Ferrari, Raffaele, Albani, Diego, Pickering-Brown, Stuart, Faber, Kelley, Kukull, Walter A., Morenas-Rodriguez, Estrella, Lleó, Alberto, Fortea, Juan, Alcolea, Daniel, Clarimon, Jordi, Nalls, Mike A., Ferrucci, Luigi, Resnick, Susan M., Tanaka, Toshiko, Foroud, Tatiana M., Graff-Radford, Neill R., Wszolek, Zbigniew K., Ferman, Tanis, Boeve, Bradley F., Hardy, John A., Topol, Eric J., Torkamani, Ali, Singleton, Andrew B., Ryten, Mina, Dickson, Dennis W., Chiò, Adriano, Ross, Owen A., Gibbs, J. Raphael, Dalgard, Clifton L., Traynor, Bryan J., and Scholz, Sonja W.
Published: 2021
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38. Post-mortem assessment in vascular dementia: advances and aspirations

Author: McAleese, Kirsty E, Alafuzoff, Irina, Charidimou, Andreas, De Reuck, Jacques, Grinberg, Lea T, Hainsworth, Atticus H, Hortobagyi, Tibor, Ince, Paul, Jellinger, Kurt, Gao, Jing, Kalaria, Raj N, Kovacs, Gabor G, Kövari, Enikö, Love, Seth, Popovic, Mara, Skrobot, Olivia, Taipa, Ricardo, Thal, Dietmar R, Werring, David, Wharton, Stephen B, and Attems, Johannes
Subjects: Health Services and Systems, Health Sciences, Alzheimer's Disease, Neurodegenerative, Brain Disorders, Aging, Acquired Cognitive Impairment, Vascular Cognitive Impairment/Dementia, Dementia, Neurosciences, Alzheimer's Disease Related Dementias (ADRD), Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Biomedical Imaging, Aetiology, 2.1 Biological and endogenous factors, Neurological, Aged, Alzheimer Disease, Autopsy, Brain, Cerebrovascular Disorders, Comorbidity, Dementia, Vascular, Humans, Prevalence, Vascular dementia, Vascular cognitive impairment, Cerebrovascular disease, Cerebrovascular lesions, Neuropathology, Magnetic resonance imaging, Post-mortem MRI, Mixed dementia, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract: BackgroundCerebrovascular lesions are a frequent finding in the elderly population. However, the impact of these lesions on cognitive performance, the prevalence of vascular dementia, and the pathophysiology behind characteristic in vivo imaging findings are subject to controversy. Moreover, there are no standardised criteria for the neuropathological assessment of cerebrovascular disease or its related lesions in human post-mortem brains, and conventional histological techniques may indeed be insufficient to fully reflect the consequences of cerebrovascular disease.DiscussionHere, we review and discuss both the neuropathological and in vivo imaging characteristics of cerebrovascular disease, prevalence rates of vascular dementia, and clinico-pathological correlations. We also discuss the frequent comorbidity of cerebrovascular pathology and Alzheimer's disease pathology, as well as the difficult and controversial issue of clinically differentiating between Alzheimer's disease, vascular dementia and mixed Alzheimer's disease/vascular dementia. Finally, we consider additional novel approaches to complement and enhance current post-mortem assessment of cerebral human tissue.ConclusionElucidation of the pathophysiology of cerebrovascular disease, clarification of characteristic findings of in vivo imaging and knowledge about the impact of combined pathologies are needed to improve the diagnostic accuracy of clinical diagnoses.
Published: 2016

39. Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy

Author: Kovacs, Gabor G, Ferrer, Isidro, Grinberg, Lea T, Alafuzoff, Irina, Attems, Johannes, Budka, Herbert, Cairns, Nigel J, Crary, John F, Duyckaerts, Charles, Ghetti, Bernardino, Halliday, Glenda M, Ironside, James W, Love, Seth, Mackenzie, Ian R, Munoz, David G, Murray, Melissa E, Nelson, Peter T, Takahashi, Hitoshi, Trojanowski, John Q, Ansorge, Olaf, Arzberger, Thomas, Baborie, Atik, Beach, Thomas G, Bieniek, Kevin F, Bigio, Eileen H, Bodi, Istvan, Dugger, Brittany N, Feany, Mel, Gelpi, Ellen, Gentleman, Stephen M, Giaccone, Giorgio, Hatanpaa, Kimmo J, Heale, Richard, Hof, Patrick R, Hofer, Monika, Hortobágyi, Tibor, Jellinger, Kurt, Jicha, Gregory A, Ince, Paul, Kofler, Julia, Kövari, Enikö, Kril, Jillian J, Mann, David M, Matej, Radoslav, McKee, Ann C, McLean, Catriona, Milenkovic, Ivan, Montine, Thomas J, Murayama, Shigeo, Lee, Edward B, Rahimi, Jasmin, Rodriguez, Roberta D, Rozemüller, Annemieke, Schneider, Julie A, Schultz, Christian, Seeley, William, Seilhean, Danielle, Smith, Colin, Tagliavini, Fabrizio, Takao, Masaki, Thal, Dietmar Rudolf, Toledo, Jon B, Tolnay, Markus, Troncoso, Juan C, Vinters, Harry V, Weis, Serge, Wharton, Stephen B, White, Charles L, Wisniewski, Thomas, Woulfe, John M, Yamada, Masahito, and Dickson, Dennis W
Subjects: Biomedical and Clinical Sciences, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Rare Diseases, Alzheimer's Disease, Aging, Frontotemporal Dementia (FTD), Brain Disorders, Dementia, Neurodegenerative, Acquired Cognitive Impairment, Neurological, Animals, Astrocytes, Brain, Humans, Neuroglia, Tauopathies, tau Proteins, ARTAG, Tau astrogliopathy, Tau, Clinical Sciences, Neurology & Neurosurgery
Abstract: Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of astroglial tau pathology in the aged brain, facilitating communication among neuropathologists and researchers, and informing interpretation of clinical biomarkers and imaging studies that focus on tau-related indicators.
Published: 2016

40. Fulminant corticobasal degeneration: a distinct variant with predominant neuronal tau aggregates

Author: Ling, Helen, Gelpi, Ellen, Davey, Karen, Jaunmuktane, Zane, Mok, Kin Y., Jabbari, Edwin, Simone, Roberto, R’Bibo, Lea, Brandner, Sebastian, Ellis, Matthew J., Attems, Johannes, Mann, David, Halliday, Glenda M., Al-Sarraj, S., Hedreen, J., Ironside, James W., Kovacs, Gabor G., Kovari, E., Love, S., Vonsattel, Jean Paul G., Allinson, Kieren S. J., Hansen, Daniela, Bradshaw, Teisha, Setó-Salvia, Núria, Wray, Selina, de Silva, Rohan, Morris, Huw R., Warner, Thomas T., Hardy, John, Holton, Janice L., and Revesz, Tamas
Published: 2020
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41. Neurodegenerative brain changes are associated with area deprivation in the United Kingdom: findings from the Brains for Dementia Research study

Author: Hamilton, Calum A., Matthews, Fiona E., Erskine, Daniel, Attems, Johannes, and Thomas, Alan J.
Published: 2021
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42. Cytosolic Trapping of a Mitochondrial Heat Shock Protein Is an Early Pathological Event in Synucleinopathies

Author: Szegő, Éva M., Dominguez-Meijide, Antonio, Gerhardt, Ellen, König, Annekatrin, Koss, David J., Li, Wen, Pinho, Raquel, Fahlbusch, Christiane, Johnson, Mary, Santos, Patricia, Villar-Piqué, Anna, Thom, Tobias, Rizzoli, Silvio, Schmitz, Matthias, Li, Jiayi, Zerr, Inga, Attems, Johannes, Jahn, Olaf, and Outeiro, Tiago F.
Published: 2019
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43. Frequency and signature of somatic variants in 1461 human brain exomes

Author: Wei, Wei, Keogh, Michael J., Aryaman, Juvid, Golder, Zoe, Kullar, Peter J., Wilson, Ian, Talbot, Kevin, Turner, Martin R., McKenzie, Chris-Anne, Troakes, Claire, Attems, Johannes, Smith, Colin, Sarraj, Safa Al, Morris, Chris M., Ansorge, Olaf, Jones, Nick S., Ironside, James W., and Chinnery, Patrick F.
Published: 2019
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44. Alzheimer's disease pathology explains association between dementia with Lewy bodies and APOE-ε4/TOMM40 long poly-T repeat allele variants

Author: Prokopenko, Inga, Miyakawa, Gentaro, Zheng, Bang, Heikkinen, Jani, Petrova Quayle, Daniela, Udeh-Momoh, Chinedu, Claringbould, Annique, Neumann, Juliane, Haytural, Hazal, Kaakinen, Marika A., Loizidou, Elena, Meissner, Esther, Bertram, Lars, Gveric, Djordje O., Gentleman, Steve M., Attems, Johannes, Perneczky, Robert, Arzberger, Thomas, Muglia, Pierandrea, Lill, Christina M., Parkkinen, Laura, and Middleton, Lefkos T.
Published: 2019
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45. Primary age-related tauopathy (PART): a common pathology associated with human aging

Author: Crary, John F, Trojanowski, John Q, Schneider, Julie A, Abisambra, Jose F, Abner, Erin L, Alafuzoff, Irina, Arnold, Steven E, Attems, Johannes, Beach, Thomas G, Bigio, Eileen H, Cairns, Nigel J, Dickson, Dennis W, Gearing, Marla, Grinberg, Lea T, Hof, Patrick R, Hyman, Bradley T, Jellinger, Kurt, Jicha, Gregory A, Kovacs, Gabor G, Knopman, David S, Kofler, Julia, Kukull, Walter A, Mackenzie, Ian R, Masliah, Eliezer, McKee, Ann, Montine, Thomas J, Murray, Melissa E, Neltner, Janna H, Santa-Maria, Ismael, Seeley, William W, Serrano-Pozo, Alberto, Shelanski, Michael L, Stein, Thor, Takao, Masaki, Thal, Dietmar R, Toledo, Jonathan B, Troncoso, Juan C, Vonsattel, Jean Paul, White, Charles L, Wisniewski, Thomas, Woltjer, Randall L, Yamada, Masahito, and Nelson, Peter T
Subjects: Biomedical and Clinical Sciences, Neurosciences, Neurodegenerative, Brain Disorders, Aging, Alzheimer's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Alzheimer's Disease Related Dementias (ADRD), Acquired Cognitive Impairment, Aetiology, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, 2.1 Biological and endogenous factors, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Brain, Diagnosis, Differential, Humans, Plaque, Amyloid, Tauopathies, Terminology as Topic, TPSD, TOD, Braak, Neuropathology, Consensus, Clinical Sciences, Neurology & Neurosurgery
Abstract: We recommend a new term, "primary age-related tauopathy" (PART), to describe a pathology that is commonly observed in the brains of aged individuals. Many autopsy studies have reported brains with neurofibrillary tangles (NFTs) that are indistinguishable from those of Alzheimer's disease (AD), in the absence of amyloid (Aβ) plaques. For these "NFT+/Aβ-" brains, for which formal criteria for AD neuropathologic changes are not met, the NFTs are mostly restricted to structures in the medial temporal lobe, basal forebrain, brainstem, and olfactory areas (bulb and cortex). Symptoms in persons with PART usually range from normal to amnestic cognitive changes, with only a minority exhibiting profound impairment. Because cognitive impairment is often mild, existing clinicopathologic designations, such as "tangle-only dementia" and "tangle-predominant senile dementia", are imprecise and not appropriate for most subjects. PART is almost universally detectable at autopsy among elderly individuals, yet this pathological process cannot be specifically identified pre-mortem at the present time. Improved biomarkers and tau imaging may enable diagnosis of PART in clinical settings in the future. Indeed, recent studies have identified a common biomarker profile consisting of temporal lobe atrophy and tauopathy without evidence of Aβ accumulation. For both researchers and clinicians, a revised nomenclature will raise awareness of this extremely common pathologic change while providing a conceptual foundation for future studies. Prior reports that have elucidated features of the pathologic entity we refer to as PART are discussed, and working neuropathological diagnostic criteria are proposed.
Published: 2014

46. Frontotemporal dementia and its subtypes: a genome-wide association study

Author: Ferrari, Raffaele, Hernandez, Dena G, Nalls, Michael A, Rohrer, Jonathan D, Ramasamy, Adaikalavan, Kwok, John BJ, 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 RA, Hsiung, Ging-Yuek R, Mann, David MA, 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 CM, 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, and Rossor, Martin N
Subjects: Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Dementia, Frontotemporal Dementia (FTD), Brain Disorders, Genetics, Clinical Research, Rare Diseases, Prevention, Acquired Cognitive Impairment, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aging, Alzheimer's Disease Related Dementias (ADRD), Human Genome, Neurodegenerative, 2.1 Biological and endogenous factors, Neurological, Adult, Aged, Aged, 80 and over, Female, Frontotemporal Dementia, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Neurology & Neurosurgery, Clinical sciences
Abstract: BackgroundFrontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72--have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.MethodsWe did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with FTD and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with FTD and 4308 controls), we did separate association analyses for each FTD subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and FTD overlapping with motor neuron disease [FTD-MND]), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p
Published: 2014

47. Associations between multimorbidity and neuropathology in dementia: consideration of functional cognitive disorders, psychiatric illness and dementia mimics.

Author: Hamilton, Calum A., Matthews, Fiona E., Attems, Johannes, Donaghy, Paul C., Erskine, Daniel, Taylor, John-Paul, and Thomas, Alan J.
Subjects: COGNITION disorders, CEREBROVASCULAR disease, ALZHEIMER'S disease, DEMENTIA, NEUROLOGICAL disorders, COMORBIDITY, MIND-wandering
Abstract: Background: Multimorbidity, the presence of two or more health conditions, has been identified as a possible risk factor for clinical dementia. It is unclear whether this is due to worsening brain health and underlying neuropathology, or other factors. In some cases, conditions may reflect the same disease process as dementia (e.g. Parkinson's disease, vascular disease), in others, conditions may reflect a prodromal stage of dementia (e.g. depression, anxiety and psychosis). Aims: To assess whether multimorbidity in later life was associated with more severe dementia-related neuropathology at autopsy. Method: We examined ante-mortem and autopsy data from 767 brain tissue donors from the UK, identifying physical multimorbidity in later life and specific brain-related conditions. We assessed associations between these purported risk factors and dementia-related neuropathological changes at autopsy (Alzheimer's-disease related neuropathology, Lewy body pathology, cerebrovascular disease and limbic-predominant age-related TDP-43 encephalopathy) with logistic models. Results: Physical multimorbidity was not associated with greater dementia-related neuropathological changes. In the presence of physical multimorbidity, clinical dementia was less likely to be associated with Alzheimer's disease pathology. Conversely, conditions which may be clinical or prodromal manifestations of dementia-related neuropathology (Parkinson's disease, cerebrovascular disease, depression and other psychiatric conditions) were associated with dementia and neuropathological changes. Conclusions: Physical multimorbidity alone is not associated with greater dementia-related neuropathological change; inappropriate inclusion of brain-related conditions in multimorbidity measures and misdiagnosis of neurodegenerative dementia may better explain increased rates of clinical dementia in multimorbidity [ABSTRACT FROM AUTHOR]
Published: 2024
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48. Prevalence of Concomitant Pathologies in Parkinson’s Disease: Implications for Prognosis, Diagnosis, and Insights into Common Pathogenic Mechanisms

Author: Walker, Lauren, primary and Attems, Johannes, additional
Published: 2023
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49. Neuropathology

Author: Attems, Johannes, primary and Jellinger, Kurt A., additional
Published: 2020
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50. Lewy body pathology is more prevalent in older individuals with mitochondrial disease than controls

Author: Erskine, Daniel, Reeve, Amy K., Polvikoski, Tuomo, Schaefer, Andrew M., Taylor, Robert W., Lax, Nichola Z., El-Agnaf, Omar, Attems, Johannes, Gorman, Gráinne S., Turnbull, Doug M., and Ng, Yi Shau
Published: 2020
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