{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T22:40:00Z","timestamp":1789771200471,"version":"4.0.1"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T00:00:00Z","timestamp":1695859200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T00:00:00Z","timestamp":1695859200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005331","name":"American Brain Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005331","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016608","name":"Rainwater Charitable Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005339","name":"American Academy of Neurology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005339","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH\u201019\u20101\u20100709"],"award-info":[{"award-number":["W81XWH\u201019\u20101\u20100709"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alz &amp;amp; Dem Diag Ass &amp;amp; Dis Mo"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Early\u2010onset Alzheimer's disease (AD) is highly heritable, yet only 10% of cases are associated with known pathogenic mutations. For early\u2010onset AD patients without an identified autosomal dominant cause, we hypothesized that their early\u2010onset disease reflects further enrichment of the common risk\u2010conferring single nucleotide polymorphisms associated with late\u2010onset AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>We applied a previously validated polygenic hazard score for late\u2010onset AD to 193 consecutive patients diagnosed at our tertiary dementia referral center with symptomatic early\u2010onset AD. For comparison, we included 179 participants with late\u2010onset AD and 70 healthy controls. Polygenic hazard scores were similar in early\u2010 versus late\u2010onset AD. The polygenic hazard score was not associated with age\u2010of\u2010onset or disease biomarkers within early\u2010onset AD. Early\u2010onset AD does not represent an extreme enrichment of the common single nucleotide polymorphisms associated with late\u2010onset AD. Further exploration of novel genetic risk factors of this highly heritable disease is warranted.<\/jats:p>\n                    <jats:sec>\n                      <jats:title>Highlights<\/jats:title>\n                      <jats:p>\n                        <jats:list list-type=\"bullet\">\n                          <jats:list-item>\n                            <jats:p>There is a unique genetic architecture of early\u2010 versus late\u2010onset Alzheimer's disease (AD).<\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>Late\u2010onset AD polygenic risk is not an explanation for early\u2010onset AD.<\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>Polygenic risk of late\u2010onset AD does not predict early\u2010onset AD biology.<\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>Unique genetic architecture of early\u2010 versus late\u2010onset AD parallels AD heterogeneity.<\/jats:p>\n                          <\/jats:list-item>\n                        <\/jats:list>\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1002\/dad2.12482","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T05:32:39Z","timestamp":1695879159000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Early\u2010onset Alzheimer's disease explained by polygenic risk of late\u2010onset disease?"],"prefix":"10.1002","volume":"15","author":[{"given":"William G.","family":"Mantyh","sequence":"first","affiliation":[{"name":"Department of Neurology University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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W.","family":"Bonham","sequence":"additional","affiliation":[{"name":"Memory and Aging Center Department of Neurology University of California San Francisco  San Francisco California USA"},{"name":"Department of Radiology and Biomedical Imaging University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashlyn G.","family":"Anderson","sequence":"additional","affiliation":[{"name":"HudsonAlpha Institute for Biotechnology  Huntsville Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel W.","family":"Sirkis","sequence":"additional","affiliation":[{"name":"Memory and Aging Center Department of Neurology University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renaud La","family":"Joie","sequence":"additional","affiliation":[{"name":"Memory and Aging Center Department of Neurology University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Iaccarino","sequence":"additional","affiliation":[{"name":"Memory and Aging Center Department of Neurology University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran","family":"Chaudhary","sequence":"additional","affiliation":[{"name":"Memory and Aging Center Department of Neurology University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Edwards","sequence":"additional","affiliation":[{"name":"Memory and Aging Center Department of Neurology University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Strom","sequence":"additional","affiliation":[{"name":"Memory and Aging Center Department of Neurology University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harli","family":"Grant","sequence":"additional","affiliation":[{"name":"Memory and Aging Center Department of Neurology University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel E.","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary A.","family":"Miller","sequence":"additional","affiliation":[{"name":"Memory and Aging Center Department of Neurology University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilu 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gil D.","family":"Rabinovici","sequence":"additional","affiliation":[{"name":"Memory and Aging Center Department of Neurology University of California San Francisco  San Francisco California USA"},{"name":"Department of Radiology and Biomedical Imaging University of California San Francisco  San Francisco California USA"},{"name":"Life Sciences Division Lawrence Berkeley National Laboratory  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer S.","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"Memory and Aging Center Department of Neurology University of California San Francisco  San Francisco California 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