{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:52:58Z","timestamp":1790729578979,"version":"4.1.0"},"reference-count":64,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["AACSF\u201022\u2010973008"],"award-info":[{"award-number":["AACSF\u201022\u2010973008"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2025,12]]},"abstract":"Abstract<\/jats:title>\n \n INTRODUCTION<\/jats:title>\n New methods estimate amyloid positivity onset age (EAOA) from amyloid positron emission tomography (PET). We explore the genetics of EAOA to identify molecular factors underlying the earliest Alzheimer's disease (AD) changes.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n Harmonized amyloid PET data from 4216 participants were used in genome\u2010wide survival, tissue\u2010specific gene expression, and genetic covariance analyses of EAOA.<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Variants in apolipoprotein E (\n APOE<\/jats:italic>\n ),\n ABCA7<\/jats:italic>\n , and\n RASGEF1C<\/jats:italic>\n associated with earlier EAOA.\n APOE<\/jats:italic>\n \u03b54\/\u03b54 and \u03b53\/\u03b54 converted 6.3 and 5 years earlier than \u03b53\/\u03b53, respectively. \u03b52 was protective against earlier EAOA. rs4147929, an expression quantitative trait locus for\n ABCA7<\/jats:italic>\n , associated with a 4 year earlier EAOA. This variant was associated with lower brain expression of\n ABCA7<\/jats:italic>\n , which was associated with increased amyloid pathology at autopsy. Multiple immune\u2010related diseases shared genetic covariance with EAOA.\n <\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n \n APOE<\/jats:italic>\n ,\n ABCA7<\/jats:italic>\n , and\n RASGEF1C<\/jats:italic>\n associated with earlier EAOA, with supporting evidence from tissue\u2010specific expression analyses, offering insights into intervenable targets at early stages of AD.\n <\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n Novel methods estimate how long ago a patient converted to amyloid positivity.<\/jats:p>\n <\/jats:list-item>\n \n Estimating this amyloid clock allows us to determine the onset of the earliest Alzheimer's disease changes.<\/jats:p>\n <\/jats:list-item>\n \n We evaluated what genes influence when someone converts to amyloid positivity.<\/jats:p>\n <\/jats:list-item>\n \n \n Apolipoprotein E (\n APOE<\/jats:italic>\n )\n , ABCA7<\/jats:italic>\n , and\n RASGEF1C<\/jats:italic>\n associated with earlier age of amyloid positivity.\n <\/jats:p>\n <\/jats:list-item>\n \n Genetic results were supported by tissue\u2010specific expression analyses.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/alz.71006","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T09:53:53Z","timestamp":1765619633000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["APOE, ABCA7<\/i>\n , and\n RASGEF1C<\/i>\n are associated with earlier onset of amyloid deposition from more than 4000 harmonized positron emission tomography images"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9480-5497","authenticated-orcid":false,"given":"Tonnar","family":"Castellano","sequence":"first","affiliation":[{"name":"Vanderbilt Memory and Alzheimer's Center Vanderbilt University Medical Center Nashville Tennessee 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