{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T10:06:03Z","timestamp":1788257163795,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.pgen.1012170","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000}}],"reference-count":84,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG062695"],"award-info":[{"award-number":["AG062695"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG062695"],"award-info":[{"award-number":["AG062695"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG019085"],"award-info":[{"award-number":["AG019085"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG032984"],"award-info":[{"award-number":["AG032984"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG036528"],"award-info":[{"award-number":["AG036528"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG041689"],"award-info":[{"award-number":["AG041689"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG016976"],"award-info":[{"award-number":["AG016976"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG026395"],"award-info":[{"award-number":["AG026395"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG041797"],"award-info":[{"award-number":["AG041797"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG008702"],"award-info":[{"award-number":["AG008702"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG015473"],"award-info":[{"award-number":["AG015473"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG010161"],"award-info":[{"award-number":["AG010161"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG027944"],"award-info":[{"award-number":["AG027944"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG010491"],"award-info":[{"award-number":["AG010491"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG021547"],"award-info":[{"award-number":["AG021547"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG019757"],"award-info":[{"award-number":["AG019757"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG066567"],"award-info":[{"award-number":["AG066567"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG0066468"],"award-info":[{"award-number":["AG0066468"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG0064877"],"award-info":[{"award-number":["AG0064877"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG007562"],"award-info":[{"award-number":["AG007562"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG023651"],"award-info":[{"award-number":["AG023651"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    Understanding the genetic foundations of dementia is critical to unraveling its complex molecular basis. Given that a clinical diagnosis of Alzheimer\u2019s disease (AD) dementia often results from interplay between multiple underlying neuropathologic co-morbidities, previous genome-wide association studies (GWAS) of clinically diagnosed AD are restricted in their ability to translate genetic associations to potential targeted therapeutics. The current study seeks to address these limitations by presenting the largest GWAS to date (n\u2009=\u200912,509) of neuropathologic hallmarks of AD and AD related dementias (ADRDs). We further performed a candidate-variant analysis using loci previously identified in GWAS of clinically diagnosed AD dementia and Parkinson\u2019s disease (PD). Finally, we conducted heritability and genetic correlation analyses using linkage disequilibrium (LD) score regression. We found broad genome-wide significant associations with\n                    <jats:italic>APOE<\/jats:italic>\n                    across AD and ADRDs but not cerebrovascular disease and vascular brain injury. We further identified 12 significant loci across 10 neuropathologic phenotypes, including 5 loci previously implicated in GWAS of clinical AD and ADRDs (variants on\n                    <jats:italic>BIN1, PICALM\/ EED, TMEM106B, GRN,<\/jats:italic>\n                    and\n                    <jats:italic>SNCA\/ SNCA-AS1<\/jats:italic>\n                    ) and 7 novel genome-wide associations (variants on\n                    <jats:italic>EPHA5, PSMG1, LINC00276, VAPA, LINC00290, DOCK4<\/jats:italic>\n                    and\n                    <jats:italic>SLAIN2\/ SLC10A4<\/jats:italic>\n                    ). Our analysis of AD and PD clinical candidate variants demonstrated several that were associated with AD neuropathologic change and Lewy body disease, as well as substantial overlap with neuropathologic lesions other than the primary neuropathologic hallmarks of these diseases. Heritability analyses demonstrated heritability that was high for amyloid plaques (78%) relative to prior clinical AD heritability analyses, intermediate for TDP-43 inclusions (41%), and low for remaining AD and ADRD pathologic features. This study underscores the importance of investigating the underlying neuropathologic hallmarks of AD and ADRDs as a step toward refining the translation of genetic associations to biomarker interpretation and development of targeted therapeutics.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1012170","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T17:40:06Z","timestamp":1782754806000},"page":"e1012170","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genome wide association study meta-analysis of neuropathologic lesions of Alzheimer\u2019s disease and related dementias in a multi-site autopsy cohort"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2139-987X","authenticated-orcid":true,"given":"Brenna","family":"Cholerton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3667-4694","authenticated-orcid":true,"given":"Dana","family":"Godrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8933-002X","authenticated-orcid":true,"given":"Jeremy","family":"Pasteris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Rivero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eden R.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9515-5157","authenticated-orcid":true,"given":"Brian W.","family":"Kunkle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam C.","family":"Naj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3748-7193","authenticated-orcid":true,"given":"Kara L.","family":"Hamilton-Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4043-5060","authenticated-orcid":true,"given":"Hui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Ping","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Logan","family":"Dumitrescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Hohman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Mayeux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric B.","family":"Larson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul K.","family":"Crane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Dirk","family":"Keene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin S.","family":"Latimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubhabrata","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia K.","family":"Kofler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Ilyas","family":"Kamboh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4068-8578","authenticated-orcid":true,"given":"Laura","family":"Molina-Porcel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Cuccaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret A.","family":"Pericak-Vance","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Rundek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9336-6404","authenticated-orcid":true,"given":"William K.","family":"Scott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Kukull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Schellenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Alzheimer\u2019s Disease Genetics Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7061-6332","authenticated-orcid":true,"given":"Gary W.","family":"Beecham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Montine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"issue":"6","key":"pgen.1012170.ref001","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.jalz.2016.09.015","article-title":"Mixed neuropathologies and estimated rates of clinical progression in a large autopsy sample","volume":"13","author":"WD Brenowitz","year":"2017","journal-title":"Alzheimers Dement"},{"issue":"2","key":"pgen.1012170.ref002","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s00401-017-1717-7","article-title":"Impact of multiple pathologies on the threshold for clinically overt dementia","volume":"134","author":"A Kapasi","year":"2017","journal-title":"Acta Neuropathol"},{"issue":"6","key":"pgen.1012170.ref003","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1212\/WNL.0000000000001831","article-title":"Multiple pathologies are common and related to dementia in the oldest-old: The 90+ Study","volume":"85","author":"CH Kawas","year":"2015","journal-title":"Neurology"},{"issue":"6","key":"pgen.1012170.ref004","doi-asserted-by":"crossref","first-page":"718","DOI":"10.2174\/156720512801322555","article-title":"Adult Changes in Thought study: dementia is an individually varying convergent syndrome with prevalent clinically silent diseases that may be modified by some commonly used therapeutics","volume":"9","author":"TJ Montine","year":"2012","journal-title":"Curr Alzheimer Res"},{"issue":"9","key":"pgen.1012170.ref005","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s13195-014-0082-1","article-title":"Prevalence of mixed pathologies in the aging brain","volume":"6","author":"J Rahimi","year":"2014","journal-title":"Alzheimers Res Ther"},{"issue":"3","key":"pgen.1012170.ref006","doi-asserted-by":"crossref","first-page":"691","DOI":"10.3233\/JAD-2009-1227","article-title":"The neuropathology of older persons with and without dementia from community versus clinic cohorts","volume":"18","author":"JA Schneider","year":"2009","journal-title":"J Alzheimers Dis"},{"issue":"11","key":"pgen.1012170.ref007","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1212\/WNL.0000000000002480","article-title":"Neuropathologic comorbidity and cognitive impairment in the Nun and Honolulu-Asia Aging Studies","volume":"86","author":"LR White","year":"2016","journal-title":"Neurology"},{"key":"pgen.1012170.ref008","doi-asserted-by":"crossref","DOI":"10.3233\/JAD-179939","article-title":"Religious Orders Study and Rush Memory and Aging Project","volume":"64","author":"DA Bennett","year":"2018","journal-title":"J Alzheimers Dis"},{"issue":"3","key":"pgen.1012170.ref009","doi-asserted-by":"crossref","DOI":"10.1093\/braincomms\/fcac125","article-title":"Genome-wide association studies for Alzheimer\u2019s disease: bigger is not always better","volume":"4","author":"V Escott-Price","year":"2022","journal-title":"Brain Commun"},{"issue":"3","key":"pgen.1012170.ref010","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41588-018-0311-9","article-title":"Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer\u2019s disease risk","volume":"51","author":"IE Jansen","year":"2019","journal-title":"Nat Genet"},{"issue":"3","key":"pgen.1012170.ref011","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/s41588-019-0358-2","article-title":"Genetic meta-analysis of diagnosed Alzheimer\u2019s disease identifies new risk loci and implicates A\u03b2, tau, immunity and lipid processing","volume":"51","author":"BW Kunkle","year":"2019","journal-title":"Nat Genet"},{"issue":"9","key":"pgen.1012170.ref012","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1038\/s41588-021-00921-z","article-title":"A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer\u2019s disease","volume":"53","author":"DP Wightman","year":"2021","journal-title":"Nat Genet"},{"issue":"2","key":"pgen.1012170.ref013","article-title":"Identification of 16 novel Alzheimer\u2019s disease loci using multi-ancestry meta-analyses","volume":"21","author":"JDS Willett","year":"2025","journal-title":"Alzheimers Dement"},{"issue":"5","key":"pgen.1012170.ref014","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1097\/NEN.0b013e31825018f7","article-title":"Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature","volume":"71","author":"PT Nelson","year":"2012","journal-title":"J Neuropathol Exp Neurol"},{"issue":"1","key":"pgen.1012170.ref015","doi-asserted-by":"crossref","first-page":"307","DOI":"10.3233\/JAD-230331","article-title":"Neuropathologic Changes of Alzheimer\u2019s Disease and Related Dementias: Relevance to Future Prevention","volume":"95","author":"LR White","year":"2023","journal-title":"J Alzheimers Dis"},{"issue":"3","key":"pgen.1012170.ref016","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1177\/13872877251317543","article-title":"Navigating the blurred boundary: Neuropathologic changes versus clinical symptoms in Alzheimer\u2019s disease, and its consequences for research in genetics","volume":"104","author":"C Xavier","year":"2025","journal-title":"J Alzheimers Dis"},{"issue":"5","key":"pgen.1012170.ref017","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1007\/s00401-022-02454-z","article-title":"Genome-wide meta-analysis for Alzheimer\u2019s disease cerebrospinal fluid biomarkers","volume":"144","author":"IE Jansen","year":"2022","journal-title":"Acta Neuropathol"},{"key":"pgen.1012170.ref018","unstructured":"Cruchaga C, Timsina J, Jiang C. GWAS meta-analysis of CSF Alzheimer\u2019s disease biomarkers 18,948 individuals reveal novel loci and genes regulating lipid metabolism, brain volume and autophagy. 2025."},{"issue":"8","key":"pgen.1012170.ref019","doi-asserted-by":"crossref","first-page":"280","DOI":"10.3390\/jimaging11080280","article-title":"The Genetics of Amyloid Deposition: A Systematic Review of Genome-Wide Association Studies Using Amyloid PET Imaging in Alzheimer\u2019s Disease","volume":"11","author":"AA Amanullah","year":"2025","journal-title":"J Imaging"},{"issue":"10","key":"pgen.1012170.ref020","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1001\/jamaneurol.2020.1760","article-title":"Association Between Common Variants in RBFOX1, an RNA-Binding Protein, and Brain Amyloidosis in Early and Preclinical Alzheimer Disease","volume":"77","author":"NS Raghavan","year":"2020","journal-title":"JAMA Neurol"},{"issue":"9","key":"pgen.1012170.ref021","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1004606","article-title":"Genome-wide association meta-analysis of neuropathologic features of Alzheimer\u2019s disease and related dementias","volume":"10","author":"GW Beecham","year":"2014","journal-title":"PLoS Genet"},{"issue":"6","key":"pgen.1012170.ref022","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1038\/mp.2017.20","article-title":"Susceptibility to neurofibrillary tangles: role of the PTPRD locus and limited pleiotropy with other neuropathologies","volume":"23","author":"LB Chibnik","year":"2018","journal-title":"Mol Psychiatry"},{"issue":"1","key":"pgen.1012170.ref023","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/S1474-4422(17)30400-3","article-title":"Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study","volume":"17","author":"R Guerreiro","year":"2018","journal-title":"Lancet Neurol"},{"issue":"6","key":"pgen.1012170.ref024","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1007\/s00401-014-1282-2","article-title":"ABCC9 gene polymorphism is associated with hippocampal sclerosis of aging pathology","volume":"127","author":"PT Nelson","year":"2014","journal-title":"Acta Neuropathol"},{"issue":"11","key":"pgen.1012170.ref025","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1038\/s41588-024-01939-9","article-title":"GWAS of multiple neuropathology endophenotypes identifies new risk loci and provides insights into the genetic risk of dementia","volume":"56","author":"LMP Shade","year":"2024","journal-title":"Nat Genet"},{"issue":"12","key":"pgen.1012170.ref026","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1002\/alz.12516","article-title":"Neuropathological lesions and their contribution to dementia and cognitive impairment in a heterogeneous clinical population","volume":"18","author":"D Godrich","year":"2022","journal-title":"Alzheimers Dement"},{"issue":"1","key":"pgen.1012170.ref027","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jalz.2011.10.007","article-title":"National Institute on Aging-Alzheimer\u2019s Association guidelines for the neuropathologic assessment of Alzheimer\u2019s disease","volume":"8","author":"BT Hyman","year":"2012","journal-title":"Alzheimers Dement"},{"issue":"12","key":"pgen.1012170.ref028","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1212\/WNL.58.12.1791","article-title":"Phases of A beta-deposition in the human brain and its relevance for the development of AD","volume":"58","author":"DR Thal","year":"2002","journal-title":"Neurology"},{"issue":"11","key":"pgen.1012170.ref029","doi-asserted-by":"crossref","DOI":"10.1002\/alz.70760","article-title":"Genome-wide association studies of TDP-43 proteinopathy and hippocampal sclerosis reveal shared genetic associations with APOE and TMEM106B","volume":"21","author":"D Godrich","year":"2025","journal-title":"Alzheimers Dement"},{"issue":"4","key":"pgen.1012170.ref030","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/s41588-022-01024-z","article-title":"New insights into the genetic etiology of Alzheimer\u2019s disease and related dementias","volume":"54","author":"C Bellenguez","year":"2022","journal-title":"Nat Genet"},{"issue":"12","key":"pgen.1012170.ref031","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/S1474-4422(19)30320-5","article-title":"Identification of novel risk loci, causal insights, and heritable risk for Parkinson\u2019s disease: a meta-analysis of genome-wide association studies","volume":"18","author":"MA Nalls","year":"2019","journal-title":"Lancet Neurol"},{"issue":"4","key":"pgen.1012170.ref032","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/s41588-018-0081-4","article-title":"Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types","volume":"50","author":"HK Finucane","year":"2018","journal-title":"Nat Genet"},{"issue":"10","key":"pgen.1012170.ref033","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1038\/ni1008-1091","article-title":"The Immunological Genome Project: networks of gene expression in immune cells","volume":"9","author":"Immunological Genome Project Consortium","year":"2008","journal-title":"Nat Immunol"},{"issue":"6","key":"pgen.1012170.ref034","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1007\/s00401-022-02421-8","article-title":"APOE4 exacerbates \u03b1-synuclein seeding activity and contributes to neurotoxicity in Alzheimer\u2019s disease with Lewy body pathology","volume":"143","author":"Y Jin","year":"2022","journal-title":"Acta Neuropathol"},{"issue":"2","key":"pgen.1012170.ref035","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1001\/jamaneurol.2013.600","article-title":"APOE \u03b54 increases risk for dementia in pure synucleinopathies","volume":"70","author":"D Tsuang","year":"2013","journal-title":"JAMA Neurol"},{"issue":"9","key":"pgen.1012170.ref036","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/S1474-4422(18)30251-5","article-title":"Evaluation of TDP-43 proteinopathy and hippocampal sclerosis in relation to APOE \u03b54 haplotype status: a community-based cohort study","volume":"17","author":"H-S Yang","year":"2018","journal-title":"Lancet Neurol"},{"issue":"1","key":"pgen.1012170.ref037","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s11065-014-9276-3","article-title":"Genetics and underlying pathology of dementia","volume":"25","author":"B Ferencz","year":"2015","journal-title":"Neuropsychol Rev"},{"issue":"2","key":"pgen.1012170.ref038","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s00401-017-1709-7","article-title":"Interactions of pathological proteins in neurodegenerative diseases","volume":"134","author":"TL Spires-Jones","year":"2017","journal-title":"Acta Neuropathol"},{"issue":"1","key":"pgen.1012170.ref039","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13024-023-00653-0","article-title":"TDP-43 pathology is associated with increased tau burdens and seeding","volume":"18","author":"SO Tom\u00e9","year":"2023","journal-title":"Mol Neurodegener"},{"key":"pgen.1012170.ref040","doi-asserted-by":"crossref","first-page":"117218","DOI":"10.1016\/j.atherosclerosis.2023.117218","article-title":"APOE and vascular disease: Sequencing and genotyping in general population cohorts","volume":"385","author":"KL Rasmussen","year":"2023","journal-title":"Atherosclerosis"},{"key":"pgen.1012170.ref041","doi-asserted-by":"crossref","first-page":"105880","DOI":"10.1016\/j.nbd.2022.105880","article-title":"Multiple gene variants linked to Alzheimer\u2019s-type clinical dementia via GWAS are also associated with non-Alzheimer\u2019s neuropathologic entities","volume":"174","author":"Y Katsumata","year":"2022","journal-title":"Neurobiol Dis"},{"issue":"1","key":"pgen.1012170.ref042","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ajhg.2016.11.007","article-title":"Genome-wide Association Study Identifies 27 Loci Influencing Concentrations of Circulating Cytokines and Growth Factors","volume":"100","author":"AV Ahola-Olli","year":"2017","journal-title":"Am J Hum Genet"},{"issue":"1","key":"pgen.1012170.ref043","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s12916-022-02399-w","article-title":"Role of circulating polyunsaturated fatty acids on cardiovascular diseases risk: analysis using Mendelian randomization and fatty acid genetic association data from over 114,000 UK Biobank participants","volume":"20","author":"MC Borges","year":"2022","journal-title":"BMC Med"},{"issue":"1","key":"pgen.1012170.ref044","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/s41467-020-20870-1","article-title":"Genome-wide association study of serum liver enzymes implicates diverse metabolic and liver pathology","volume":"12","author":"VL Chen","year":"2021","journal-title":"Nat Commun"},{"issue":"7890","key":"pgen.1012170.ref045","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/s41586-021-04064-3","article-title":"The power of genetic diversity in genome-wide association studies of lipids","volume":"600","author":"SE Graham","year":"2021","journal-title":"Nature"},{"issue":"2","key":"pgen.1012170.ref046","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3001547","article-title":"Characterising metabolomic signatures of lipid-modifying therapies through drug target mendelian randomisation","volume":"20","author":"TG Richardson","year":"2022","journal-title":"PLoS Biol"},{"issue":"3","key":"pgen.1012170.ref047","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1003062","article-title":"Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: A multivariable Mendelian randomisation analysis","volume":"17","author":"TG Richardson","year":"2020","journal-title":"PLoS Med"},{"issue":"7","key":"pgen.1012170.ref048","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1038\/s41562-023-01579-9","article-title":"Participation bias in the UK Biobank distorts genetic associations and downstream analyses","volume":"7","author":"T Schoeler","year":"2023","journal-title":"Nat Hum Behav"},{"issue":"1","key":"pgen.1012170.ref049","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.1038\/s41467-018-04362-x","article-title":"Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function","volume":"9","author":"G Davies","year":"2018","journal-title":"Nat Commun"},{"issue":"8","key":"pgen.1012170.ref050","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/s41588-018-0147-3","article-title":"Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals","volume":"50","author":"JJ Lee","year":"2018","journal-title":"Nat Genet"},{"issue":"5","key":"pgen.1012170.ref051","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/ng.803","article-title":"Common variants at ABCA7, MS4A6A\/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer\u2019s disease","volume":"43","author":"P Hollingworth","year":"2011","journal-title":"Nature Genetics"},{"issue":"5","key":"pgen.1012170.ref052","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/ng.801","article-title":"Common variants at MS4A4\/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer\u2019s disease","volume":"43","author":"AC Naj","year":"2011","journal-title":"Nat Genet"},{"issue":"2","key":"pgen.1012170.ref053","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.brainresrev.2005.02.001","article-title":"Functions of ephrin\/Eph interactions in the development of the nervous system: emphasis on the hippocampal system","volume":"49","author":"A Mart\u00ednez","year":"2005","journal-title":"Brain Res Brain Res Rev"},{"issue":"3","key":"pgen.1012170.ref054","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.conb.2009.04.009","article-title":"Synapse development and plasticity: roles of ephrin\/Eph receptor signaling","volume":"19","author":"K-O Lai","year":"2009","journal-title":"Curr Opin Neurobiol"},{"key":"pgen.1012170.ref055","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkae1070","article-title":"The NHGRI-EBI GWAS Catalog: standards for reusability, sustainability and diversity","volume":"53","author":"M Cerezo","year":"2025","journal-title":"Nucleic Acids Res"},{"issue":"7","key":"pgen.1012170.ref056","doi-asserted-by":"crossref","first-page":"3148","DOI":"10.1002\/alz.12927","article-title":"Identification of novel genes for age-at-onset of Alzheimer\u2019s disease by combining quantitative and survival trait analyses","volume":"19","author":"Y-J Li","year":"2023","journal-title":"Alzheimers Dement"},{"issue":"7757","key":"pgen.1012170.ref057","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41586-019-1140-4","article-title":"SR-B1 drives endothelial cell LDL transcytosis via DOCK4 to promote atherosclerosis","volume":"569","author":"L Huang","year":"2019","journal-title":"Nature"},{"issue":"1","key":"pgen.1012170.ref058","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s13195-021-00773-z","article-title":"Multi-trait association studies discover pleiotropic loci between Alzheimer\u2019s disease and cardiometabolic traits","volume":"13","author":"VA Million Veteran Program","year":"2021","journal-title":"Alzheimers Res Ther"},{"issue":"8","key":"pgen.1012170.ref059","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.2174\/1386207326666230912094101","article-title":"DOCK4 is a Novel Prognostic Biomarker and Correlated with Immune Infiltrates in Colon Adenocarcinoma","volume":"27","author":"X Xie","year":"2024","journal-title":"Comb Chem High Throughput Screen"},{"issue":"1","key":"pgen.1012170.ref060","doi-asserted-by":"crossref","first-page":"7973","DOI":"10.1038\/s41467-022-35553-2","article-title":"Genomics and phenomics of body mass index reveals a complex disease network","volume":"13","author":"J Huang","year":"2022","journal-title":"Nat Commun"},{"issue":"2","key":"pgen.1012170.ref061","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1111\/j.1744-313X.2012.01141.x","article-title":"Genetic associations with C-reactive protein level and white blood cell count in the KARE study","volume":"40","author":"M Kong","year":"2013","journal-title":"Int J Immunogenet"},{"issue":"12","key":"pgen.1012170.ref062","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1038\/s41588-020-00713-x","article-title":"Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals","volume":"52","author":"P Surendran","year":"2020","journal-title":"Nat Genet"},{"key":"pgen.1012170.ref063","doi-asserted-by":"crossref","first-page":"164","DOI":"10.3389\/fnins.2019.00164","article-title":"Clusterin in Alzheimer\u2019s Disease: Mechanisms, Genetics, and Lessons From Other Pathologies","volume":"13","author":"EM Foster","year":"2019","journal-title":"Front Neurosci"},{"issue":"6","key":"pgen.1012170.ref064","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1007\/s00401-016-1652-z","article-title":"Genome-wide, high-content siRNA screening identifies the Alzheimer\u2019s genetic risk factor FERMT2 as a major modulator of APP metabolism","volume":"133","author":"J Chapuis","year":"2017","journal-title":"Acta Neuropathol"},{"key":"pgen.1012170.ref065","doi-asserted-by":"crossref","first-page":"674318","DOI":"10.3389\/fnagi.2021.674318","article-title":"Similar Genetic Architecture of Alzheimer\u2019s Disease and Differential APOE Effect Between Sexes","volume":"13","author":"H Wang","year":"2021","journal-title":"Front Aging Neurosci"},{"issue":"1","key":"pgen.1012170.ref066","doi-asserted-by":"crossref","first-page":"4799","DOI":"10.1038\/s41467-020-18534-1","article-title":"Risk prediction of late-onset Alzheimer\u2019s disease implies an oligogenic architecture","volume":"11","author":"Q Zhang","year":"2020","journal-title":"Nat Commun"},{"issue":"22","key":"pgen.1012170.ref067","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1093\/bioinformatics\/btq559","article-title":"Robust relationship inference in genome-wide association studies","volume":"26","author":"A Manichaikul","year":"2010","journal-title":"Bioinformatics"},{"issue":"24","key":"pgen.1012170.ref068","doi-asserted-by":"crossref","first-page":"3326","DOI":"10.1093\/bioinformatics\/bts606","article-title":"A high-performance computing toolset for relatedness and principal component analysis of SNP data","volume":"28","author":"X Zheng","year":"2012","journal-title":"Bioinformatics"},{"issue":"7845","key":"pgen.1012170.ref069","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/s41586-021-03205-y","article-title":"Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program","volume":"590","author":"D Taliun","year":"2021","journal-title":"Nature"},{"issue":"4","key":"pgen.1012170.ref070","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1002\/gepi.21896","article-title":"Robust inference of population structure for ancestry prediction and correction of stratification in the presence of relatedness","volume":"39","author":"MP Conomos","year":"2015","journal-title":"Genet Epidemiol"},{"issue":"1","key":"pgen.1012170.ref071","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00401-011-0910-3","article-title":"National Institute on Aging-Alzheimer\u2019s Association guidelines for the neuropathologic assessment of Alzheimer\u2019s disease: a practical approach","volume":"123","author":"TJ Montine","year":"2012","journal-title":"Acta Neuropathol"},{"issue":"5","key":"pgen.1012170.ref072","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1002\/ana.410300503","article-title":"Cerebral amyloid angiopathy without and with cerebral hemorrhages: a comparative histological study","volume":"30","author":"JP Vonsattel","year":"1991","journal-title":"Ann Neurol"},{"key":"pgen.1012170.ref073","unstructured":"R Core Team. R: A Language and Environment for Statistical Computing. 2025. https:\/\/www.R-project.org"},{"issue":"4","key":"pgen.1012170.ref074","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1198\/000313002533","article-title":"Corrgrams","volume":"56","author":"M Friendly","year":"2002","journal-title":"The American Statistician"},{"issue":"9","key":"pgen.1012170.ref075","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1093\/bioinformatics\/btw079","article-title":"RVTESTS: an efficient and comprehensive tool for rare variant association analysis using sequence data","volume":"32","author":"X Zhan","year":"2016","journal-title":"Bioinformatics"},{"key":"pgen.1012170.ref076","author":"RH Christensen","year":"2023"},{"issue":"17","key":"pgen.1012170.ref077","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1093\/bioinformatics\/btq340","article-title":"METAL: fast and efficient meta-analysis of genomewide association scans","volume":"26","author":"CJ Willer","year":"2010","journal-title":"Bioinformatics"},{"issue":"25","key":"pgen.1012170.ref078","doi-asserted-by":"crossref","first-page":"731","DOI":"10.21105\/joss.00731","article-title":"qqman: an R package for visualizing GWAS results using Q-Q and manhattan plots","volume":"3","author":"S D. Turner","year":"2018","journal-title":"JOSS"},{"key":"pgen.1012170.ref079","doi-asserted-by":"crossref","DOI":"10.1007\/978-0-387-98141-3","volume-title":"Ggplot2: Elegant Graphics for Data","author":"H Wickham","year":"2009"},{"issue":"18","key":"pgen.1012170.ref080","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1093\/bioinformatics\/btq419","article-title":"LocusZoom: regional visualization of genome-wide association scan results","volume":"26","author":"RJ Pruim","year":"2010","journal-title":"Bioinformatics"},{"issue":"1","key":"pgen.1012170.ref081","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1038\/s41467-017-01261-5","article-title":"Functional mapping and annotation of genetic associations with FUMA","volume":"8","author":"K Watanabe","year":"2017","journal-title":"Nat Commun"},{"issue":"3","key":"pgen.1012170.ref082","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/ng.2892","article-title":"A general framework for estimating the relative pathogenicity of human genetic variants","volume":"46","author":"M Kircher","year":"2014","journal-title":"Nat Genet"},{"issue":"9","key":"pgen.1012170.ref083","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1101\/gr.137323.112","article-title":"Annotation of functional variation in personal genomes using RegulomeDB","volume":"22","author":"AP Boyle","year":"2012","journal-title":"Genome Res"},{"issue":"3","key":"pgen.1012170.ref084","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/ng.3211","article-title":"LD Score regression distinguishes confounding from polygenicity in genome-wide association studies","volume":"47","author":"Schizophrenia Working Group of the Psychiatric Genomics Consortium","year":"2015","journal-title":"Nat Genet"}],"updated-by":[{"DOI":"10.1371\/journal.pgen.1012170","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000}}],"container-title":["PLOS Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1012170","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T17:42:16Z","timestamp":1783446136000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1012170"}},"subtitle":[],"editor":[{"given":"J. Nicholas","family":"Cochran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,6,29]]},"references-count":84,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1012170","relation":{},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,29]]}}}