المؤلفون: Ho, Pei‐Chuan, Yu, Wai Haung, Tee, Boon Lead, Lee, Wan‐Ping, Li, Clara, Gu, Yian, Yokoyama, Jennifer S, Reyes‐Dumeyer, Dolly, Choi, Yun‐Beom, Yang, Hyun‐Sik, Vardarajan, Badri N, Tzuang, Marian, Lieu, Kevin, Lu, Anna, Faber, Kelley M, Potter, Zoë D, Revta, Carolyn, Kirsch, Maureen, McCallum, Jake, Mei, Diana, Booth, Briana, Cantwell, Laura B, Chen, Fangcong, Chou, Sephera, Clark, Dewi, Deng, Michelle, Hong, Ting Hei, Hwang, Ling‐Jen, Jiang, Lilly, Joo, Yoonmee, Kang, Younhee, Kim, Ellen S, Kim, Hoowon, Kim, Kyungmin, Kuzma, Amanda B, Lam, Eleanor, Lanata, Serggio C, Lee, Kunho, Li, Donghe, Li, Mingyao, Li, Xiang, Liu, Chia‐Lun, Liu, Collin, Liu, Linghsi, Lupo, Jody‐Lynn, Nguyen, Khai, Pfleuger, Shannon E, Qian, James, Qian, Winnie, Ramirez, Veronica, Russ, Kristen A, Seo, Eun Hyun, Song, Yeunjoo E, Tartaglia, Maria Carmela, Tian, Lu, Torres, Mina, Vo, Namkhue, Wong, Ellen C, Xie, Yuan, Yau, Eugene B, Yi, Isabelle, Yu, Victoria, Zeng, Xiaoyi, St George‐Hyslop, Peter, Au, Rhoda, Schellenberg, Gerard D, Dage, Jeffrey L, Varma, Rohit, Hsiung, Ging‐Yuek R, Rosen, Howard, Henderson, Victor W, Foroud, Tatiana, Kukull, Walter A, Peavy, Guerry M, Lee, Haeok, Feldman, Howard H, Mayeux, Richard, Chui, Helena, Jun, Gyungah R, Park, Van M Ta, Chow, Tiffany W, Wang, Li‐San

المصدر: Alzheimer's & Dementia. 20(3)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Brain Disorders, Acquired Cognitive Impairment, Clinical Trials and Supportive Activities, Alzheimer's Disease, Dementia, Minority Health, Health Disparities, Clinical Research, Prevention, Aging, Genetics, Neurological, Humans, Alzheimer Disease, Pilot Projects, Asian, Canada, Risk Factors, North American People, Alzheimer's disease, biosamples, community-based participatory research, dementia, environmental, genetics, Geriatrics, Clinical sciences, Biological psychology

الوصف: IntroductionClinical research in Alzheimer's disease (AD) lacks cohort diversity despite being a global health crisis. The Asian Cohort for Alzheimer's Disease (ACAD) was formed to address underrepresentation of Asians in research, and limited understanding of how genetics and non-genetic/lifestyle factors impact this multi-ethnic population.MethodsThe ACAD started fully recruiting in October 2021 with one central coordination site, eight recruitment sites, and two analysis sites. We developed a comprehensive study protocol for outreach and recruitment, an extensive data collection packet, and a centralized data management system, in English, Chinese, Korean, and Vietnamese.ResultsACAD has recruited 606 participants with an additional 900 expressing interest in enrollment since program inception.DiscussionACAD's traction indicates the feasibility of recruiting Asians for clinical research to enhance understanding of AD risk factors. ACAD will recruit > 5000 participants to identify genetic and non-genetic/lifestyle AD risk factors, establish blood biomarker levels for AD diagnosis, and facilitate clinical trial readiness.HighlightsThe Asian Cohort for Alzheimer's Disease (ACAD) promotes awareness of under-investment in clinical research for Asians. We are recruiting Asian Americans and Canadians for novel insights into Alzheimer's disease. We describe culturally appropriate recruitment strategies and data collection protocol. ACAD addresses challenges of recruitment from heterogeneous Asian subcommunities. We aim to implement a successful recruitment program that enrolls across three Asian subcommunities.

الوصول الحر: https://escholarship.org/uc/item/2nc0c78kTest

المؤلفون: Donghui Yan, Bowen Hu, Burcu F Darst, Shubhabrata Mukherjee, Brian W Kunkle, Yuetiva Deming, Logan Dumitrescu, Yunling Wang, Adam Naj, Amanda Kuzma, Yi Zhao, Hyunseung Kang, Sterling C Johnson, Cruchaga Carlos, Timothy J Hohman, Paul K Crane, Corinne D Engelman, Alzheimer’s Disease Genetics Consortium (ADGC), Qiongshi Lu

المصدر: eLife, Vol 12 (2024)

مصطلحات موضوعية: Alzheimer's disease, GWAS, UK-biobank, Medicine, Science, Biology (General), QH301-705.5

الوصف: Rich data from large biobanks, coupled with increasingly accessible association statistics from genome-wide association studies (GWAS), provide great opportunities to dissect the complex relationships among human traits and diseases. We introduce BADGERS, a powerful method to perform polygenic score-based biobank-wide association scans. Compared to traditional approaches, BADGERS uses GWAS summary statistics as input and does not require multiple traits to be measured in the same cohort. We applied BADGERS to two independent datasets for late-onset Alzheimer’s disease (AD; n=61,212). Among 1738 traits in the UK biobank, we identified 48 significant associations for AD. Family history, high cholesterol, and numerous traits related to intelligence and education showed strong and independent associations with AD. Furthermore, we identified 41 significant associations for a variety of AD endophenotypes. While family history and high cholesterol were strongly associated with AD subgroups and pathologies, only intelligence and education-related traits predicted pre-clinical cognitive phenotypes. These results provide novel insights into the distinct biological processes underlying various risk factors for AD.

وصف الملف: electronic resource

العلاقة: https://elifesciences.org/articles/91360Test; https://doaj.org/toc/2050-084XTest

الوصول الحر: https://doaj.org/article/70e5d04b97aa44e69655821a17499202Test

المؤلفون: Anna Mengr, Veronika Strnadová, Štěpán Strnad, Vladimír Vrkoslav, Helena Pelantová, Marek Kuzma, Thomas Comptdaer, Blanka Železná, Jaroslav Kuneš, Marie-Christine Galas, Andrea Pačesová, Lenka Maletínská

المصدر: Nutrients, Vol 15, Iss 17, p 3690 (2023)

مصطلحات موضوعية: insulin resistance, glucose intolerance, inflammation, neuroinflammation, obesity, Alzheimer’s disease, Nutrition. Foods and food supply, TX341-641

الوصف: Alzheimer’s disease (AD) is a progressive brain disorder characterized by extracellular amyloid-β (Aβ) plaques, intracellular neurofibrillary tangles formed by hyperphosphorylated Tau protein and neuroinflammation. Previous research has shown that obesity and type 2 diabetes mellitus, underlined by insulin resistance (IR), are risk factors for neurodegenerative disorders. In this study, obesity-induced peripheral and central IR and inflammation were studied in relation to AD-like pathology in the brains and periphery of APP/PS1 mice, a model of Aβ pathology, fed a high-fat diet (HFD). APP/PS1 mice and their wild-type controls fed either a standard diet or HFD were characterized at the ages of 3, 6 and 10 months by metabolic parameters related to obesity via mass spectroscopy, nuclear magnetic resonance, immunoblotting and immunohistochemistry to quantify how obesity affected AD pathology. The HFD induced substantial peripheral IR leading to central IR. APP/PS1-fed HFD mice had more pronounced IR, glucose intolerance and liver steatosis than their WT controls. The HFD worsened Aβ pathology in the hippocampi of APP/PS1 mice and significantly supported both peripheral and central inflammation. This study reveals a deleterious effect of obesity-related mild peripheral inflammation and prediabetes on the development of Aβ and Tau pathology and neuroinflammation in APP/PS1 mice.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2072-6643/15/17/3690Test; https://doaj.org/toc/2072-6643Test

الوصول الحر: https://doaj.org/article/111b0bdd0d9a4f34b2a55a3b8e5e681bTest

المؤلفون: Kunkle, Brian W, Grenier-Boley, Benjamin, Sims, Rebecca, Bis, Joshua C, Damotte, Vincent, Naj, Adam C, Boland, Anne, Vronskaya, Maria, van der Lee, Sven J, Amlie-Wolf, Alexandre, Bellenguez, Céline, Frizatti, Aura, Chouraki, Vincent, Martin, Eden R, Sleegers, Kristel, Badarinarayan, Nandini, Jakobsdottir, Johanna, Hamilton-Nelson, Kara L, Moreno-Grau, Sonia, Olaso, Robert, Raybould, Rachel, Chen, Yuning, Kuzma, Amanda B, Hiltunen, Mikko, Morgan, Taniesha, Ahmad, Shahzad, Vardarajan, Badri N, Epelbaum, Jacques, Hoffmann, Per, Boada, Merce, Beecham, Gary W, Garnier, Jean-Guillaume, Harold, Denise, Fitzpatrick, Annette L, Valladares, Otto, Moutet, Marie-Laure, Gerrish, Amy, Smith, Albert V, Qu, Liming, Bacq, Delphine, Denning, Nicola, Jian, Xueqiu, Zhao, Yi, Del Zompo, Maria, Fox, Nick C, Choi, Seung-Hoan, Mateo, Ignacio, Hughes, Joseph T, Adams, Hieab H, Malamon, John, Sanchez-Garcia, Florentino, Patel, Yogen, Brody, Jennifer A, Dombroski, Beth A, Naranjo, Maria Candida Deniz, Daniilidou, Makrina, Eiriksdottir, Gudny, Mukherjee, Shubhabrata, Wallon, David, Uphill, James, Aspelund, Thor, Cantwell, Laura B, Garzia, Fabienne, Galimberti, Daniela, Hofer, Edith, Butkiewicz, Mariusz, Fin, Bertrand, Scarpini, Elio, Sarnowski, Chloe, Bush, Will S, Meslage, Stéphane, Kornhuber, Johannes, White, Charles C, Song, Yuenjoo, Barber, Robert C, Engelborghs, Sebastiaan, Sordon, Sabrina, Voijnovic, Dina, Adams, Perrie M, Vandenberghe, Rik, Mayhaus, Manuel, Cupples, L Adrienne, Albert, Marilyn S, De Deyn, Peter P, Gu, Wei, Himali, Jayanadra J, Beekly, Duane, Squassina, Alessio, Hartmann, Annette M, Orellana, Adelina, Blacker, Deborah, Rodriguez-Rodriguez, Eloy, Lovestone, Simon, Garcia, Melissa E, Doody, Rachelle S, Munoz-Fernadez, Carmen, Sussams, Rebecca, Lin, Honghuang, Fairchild, Thomas J, Benito, Yolanda A

المصدر: Nature Genetics. 51(3)

مصطلحات موضوعية: Biochemistry and Cell Biology, Genetics, Biological Sciences, Neurodegenerative, Dementia, Alzheimer's Disease, Aging, Prevention, Brain Disorders, Neurosciences, Clinical Research, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Human Genome, Acquired Cognitive Impairment, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Neurological, Aged, Alzheimer Disease, Amyloid beta-Peptides, Case-Control Studies, Female, Genetic Loci, Genetic Predisposition to Disease, Genetic Testing, Genome-Wide Association Study, Haplotypes, Humans, Immunity, Lipid Metabolism, Lipids, Male, tau Proteins, Alzheimer Disease Genetics Consortium (ADGC), European Alzheimer’s Disease Initiative (EADI), Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE), Genetic and Environmental Risk in AD/Defining Genetic, Polygenic and Environmental Risk for Alzheimer’s Disease Consortium (GERAD/PERADES), Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology

الوصف: Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10-7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/76h3d5wdTest

المؤلفون: Peloso, Gina M, van der Lee, Sven J, Project, International Genomics of Alzheimer's, Sims, R, van der Lee, SJ, Naj, AC, Bellenguez, C, Badarinarayan, N, Jakobsdottir, J, Kunkle, BW, Boland, A, Raybould, R, Bis, JC, Martin, ER, Grenier‐Boley, B, Heilmann‐Heimbach, S, Chouraki, V, Kuzma, AB, Sleegers, K, Vronskaya, M, Ruiz, A, Graham, RR, Olaso, R, Hoffmann, P, Grove, ML, Vardarajan, BN, Hiltunen, M, Nöthen, MM, White, CC, Hamilton‐Nelson, KL, Epelbaum, J, Maier, W, Choi, SH, Beecham, GW, Dulary, C, Herms, S, Smith, AV, Funk, CC, Derbois, Forstner, AJ, Ahmad, S, Li, H, Bacq, D, Harold, D, Satizabal, CL, Valladares, O, Squassina, A, Thomas, R, Brody, JA, Qu, L, Sánchez‐Juan, P, Morgan, T, Wolters, FJ, Zhao, Y, Garcia, FS, Denning, N, Fornage, M, Malamon, J, Naranjo, MCD, Majounie, E, Mosley, TH, Dombroski, B, Wallon, D, Lupton, MK, Dupuis, J, Whitehead, P, Fratiglioni, L, Medway, C, Jian, X, Mukherjee, S, Keller, L, Brown, K, Lin, H, Cantwell, LB, Panza, F, McGuinness, B, Moreno‐Grau, S, Burgess, JD, Solfrizzi, V, Proitsi, P, Adams, HH, Allen, M, Seripa, D, Pastor, P, Cupples, LA, Price, ND, Hannequin, D, Frank‐García, A, Levy, D, Chakrabarty, P, Caffarra, P, Giegling, I, Beiser, AS, Giedraitis, V, Hampel, H, Garcia, ME, Wang, X, Lannfelt, L, Mecocci, P, Eiriksdottir, G

المصدر: Alzheimer's & Dementia Diagnosis Assessment & Disease Monitoring. 10(1)

مصطلحات موضوعية: Biological Psychology, Biomedical and Clinical Sciences, Neurosciences, Psychology, Dementia, Atherosclerosis, Alzheimer's Disease, Aging, Genetics, Acquired Cognitive Impairment, Neurodegenerative, Prevention, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Cardiovascular, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Neurological, International Genomics of Alzheimer's Project, Cholesteryl ester transfer protein, HDL-C, Instrumental variables, Single nucleotide polymorphisms, Biological psychology

الوصف: IntroductionThere is conflicting evidence whether high-density lipoprotein cholesterol (HDL-C) is a risk factor for Alzheimer's disease (AD) and dementia. Genetic variation in the cholesteryl ester transfer protein (CETP) locus is associated with altered HDL-C. We aimed to assess AD risk by genetically predicted HDL-C.MethodsTen single nucleotide polymorphisms within the CETP locus predicting HDL-C were applied to the International Genomics of Alzheimer's Project (IGAP) exome chip stage 1 results in up 16,097 late onset AD cases and 18,077 cognitively normal elderly controls. We performed instrumental variables analysis using inverse variance weighting, weighted median, and MR-Egger.ResultsBased on 10 single nucleotide polymorphisms distinctly predicting HDL-C in the CETP locus, we found that HDL-C was not associated with risk of AD (P > .7).DiscussionOur study does not support the role of HDL-C on risk of AD through HDL-C altered by CETP. This study does not rule out other mechanisms by which HDL-C affects risk of AD.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2x58666wTest
https://escholarship.org/content/qt2x58666w/qt2x58666w.pdfTest

المؤلفون: Sims, Rebecca, van der Lee, Sven J, Naj, Adam C, Bellenguez, Céline, Badarinarayan, Nandini, Jakobsdottir, Johanna, Kunkle, Brian W, Boland, Anne, Raybould, Rachel, Bis, Joshua C, Martin, Eden R, Grenier-Boley, Benjamin, Heilmann-Heimbach, Stefanie, Chouraki, Vincent, Kuzma, Amanda B, Sleegers, Kristel, Vronskaya, Maria, Ruiz, Agustin, Graham, Robert R, Olaso, Robert, Hoffmann, Per, Grove, Megan L, Vardarajan, Badri N, Hiltunen, Mikko, Nöthen, Markus M, White, Charles C, Hamilton-Nelson, Kara L, Epelbaum, Jacques, Maier, Wolfgang, Choi, Seung-Hoan, Beecham, Gary W, Dulary, Cécile, Herms, Stefan, Smith, Albert V, Funk, Cory C, Derbois, Céline, Forstner, Andreas J, Ahmad, Shahzad, Li, Hongdong, Bacq, Delphine, Harold, Denise, Satizabal, Claudia L, Valladares, Otto, Squassina, Alessio, Thomas, Rhodri, Brody, Jennifer A, Qu, Liming, Sánchez-Juan, Pascual, Morgan, Taniesha, Wolters, Frank J, Zhao, Yi, Garcia, Florentino Sanchez, Denning, Nicola, Fornage, Myriam, Malamon, John, Naranjo, Maria Candida Deniz, Majounie, Elisa, Mosley, Thomas H, Dombroski, Beth, Wallon, David, Lupton, Michelle K, Dupuis, Josée, Whitehead, Patrice, Fratiglioni, Laura, Medway, Christopher, Jian, Xueqiu, Mukherjee, Shubhabrata, Keller, Lina, Brown, Kristelle, Lin, Honghuang, Cantwell, Laura B, Panza, Francesco, McGuinness, Bernadette, Moreno-Grau, Sonia, Burgess, Jeremy D, Solfrizzi, Vincenzo, Proitsi, Petra, Adams, Hieab H, Allen, Mariet, Seripa, Davide, Pastor, Pau, Cupples, L Adrienne, Price, Nathan D, Hannequin, Didier, Frank-García, Ana, Levy, Daniel, Chakrabarty, Paramita, Caffarra, Paolo, Giegling, Ina, Beiser, Alexa S, Giedraitis, Vilmantas, Hampel, Harald, Garcia, Melissa E, Wang, Xue, Lannfelt, Lars, Mecocci, Patrizia, Eiriksdottir, Gudny, Crane, Paul K, Pasquier, Florence, Boccardi, Virginia

المصدر: Nature genetics. 49(9)

مصطلحات موضوعية: ARUK Consortium, GERAD/PERADES, CHARGE, ADGC, EADI, Microglia, Humans, Alzheimer Disease, Genetic Predisposition to Disease, Adaptor Proteins, Signal Transducing, Membrane Glycoproteins, Receptors, Immunologic, Odds Ratio, Case-Control Studies, Gene Expression Profiling, Amino Acid Sequence, Sequence Homology, Amino Acid, Gene Frequency, Genotype, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Phospholipase C gamma, Immunity, Innate, Protein Interaction Maps, Exome, Neurodegenerative, Brain Disorders, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Alzheimer's Disease, Aging, Acquired Cognitive Impairment, 2.1 Biological and endogenous factors, Developmental Biology, Biological Sciences, Medical and Health Sciences

الوصف: We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10-10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10-14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

الوصول الحر: https://escholarship.org/uc/item/5t21d2b1Test

المؤلفون: Greenfest‐Allen, Emily, Valladares, Otto, Kuksa, Pavel P., Gangadharan, Prabhakaran, Lee, Wan‐Ping, Cifello, Jeffrey, Katanic, Zivadin, Kuzma, Amanda B., Wheeler, Nicholas, Bush, William S., Leung, Yuk Yee, Schellenberg, Gerard, Stoeckert, Christian J., Wang, Li‐San

المصدر: Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Feb2024, Vol. 20 Issue 2, p1123-1136, 14p

مستخلص: INTRODUCTION: The National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site Alzheimer's Genomics Database (GenomicsDB) is a public knowledge base of Alzheimer's disease (AD) genetic datasets and genomic annotations. METHODS: GenomicsDB uses a custom systems architecture to adopt and enforce rigorous standards that facilitate harmonization of AD‐relevant genome‐wide association study summary statistics datasets with functional annotations, including over 230 million annotated variants from the AD Sequencing Project. RESULTS: GenomicsDB generates interactive reports compiled from the harmonized datasets and annotations. These reports contextualize AD‐risk associations in a broader functional genomic setting and summarize them in the context of functionally annotated genes and variants. DISCUSSION: Created to make AD‐genetics knowledge more accessible to AD researchers, the GenomicsDB is designed to guide users unfamiliar with genetic data in not only exploring but also interpreting this ever‐growing volume of data. Scalable and interoperable with other genomics resources using data technology standards, the GenomicsDB can serve as a central hub for research and data analysis on AD and related dementias. Highlights: The National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) offers to the public a unique, disease‐centric collection of AD‐relevant GWAS summary statistics datasets.Interpreting these data is challenging and requires significant bioinformatics expertise to standardize datasets and harmonize them with functional annotations on genome‐wide scales.The NIAGADS Alzheimer's GenomicsDB helps overcome these challenges by providing a user‐friendly public knowledge base for AD‐relevant genetics that shares harmonized, annotated summary statistics datasets from the NIAGADS repository in an interpretable, easily searchable format. [ABSTRACT FROM AUTHOR]

: Copyright of Alzheimer's & Dementia: The Journal of the Alzheimer's Association is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Ray, Nicholas R., Ayodele, Temitope, Jean‐Francois, Melissa, Baez, Penelope, Fernandez, Victoria, Bradley, Joseph, Crane, Paul K., Dalgard, Clifton L., Kuzma, Amanda, Nicaretta, Heather, Sims, Rebecca, Williams, Julie, Cuccaro, Michael L., Pericak‐Vance, Margaret A., Mayeux, Richard, Wang, Li‐San, Schellenberg, Gerard D., Cruchaga, Carlos, Beecham, Gary W., Reitz, Christiane

المصدر: Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Sep2023, Vol. 19 Issue 9, p4187-4195, 9p

مستخلص: INTRODUCTION: Sequencing efforts to identify genetic variants and pathways underlying Alzheimer's disease (AD) have largely focused on late‐onset AD although early‐onset AD (EOAD), accounting for ∼10% of cases, is largely unexplained by known mutations, resulting in a lack of understanding of its molecular etiology. METHODS: Whole‐genome sequencing and harmonization of clinical, neuropathological, and biomarker data of over 5000 EOAD cases of diverse ancestries. RESULTS: A publicly available genomics resource for EOAD with extensive harmonized phenotypes. Primary analysis will (1) identify novel EOAD risk loci and druggable targets; (2) assess local‐ancestry effects; (3) create EOAD prediction models; and (4) assess genetic overlap with cardiovascular and other traits. DISCUSSION: This novel resource complements over 50,000 control and late‐onset AD samples generated through the Alzheimer's Disease Sequencing Project (ADSP). The harmonized EOAD/ADSP joint call will be available through upcoming ADSP data releases and will allow for additional analyses across the full onset range. Highlights: Sequencing efforts to identify genetic variants and pathways underlying Alzheimer's disease (AD) have largely focused on late‐onset AD although early‐onset AD (EOAD), accounting for ∼10% of cases, is largely unexplained by known mutations. This results in a significant lack of understanding of the molecular etiology of this devastating form of the disease.The Early‐Onset Alzheimer's Disease Whole‐genome Sequencing Project is a collaborative initiative to generate a large‐scale genomics resource for early‐onset Alzheimer's disease with extensive harmonized phenotype data.Primary analyses are designed to (1) identify novel EOAD risk and protective loci and druggable targets; (2) assess local‐ancestry effects; (3) create EOAD prediction models; and (4) assess genetic overlap with cardiovascular and other traits.The harmonized genomic and phenotypic data from this initiative will be available through NIAGADS. [ABSTRACT FROM AUTHOR]

: Copyright of Alzheimer's & Dementia: The Journal of the Alzheimer's Association is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)