{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:05:37Z","timestamp":1792037137117,"version":"4.4.0"},"reference-count":55,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U01\u2010AG6057195"],"award-info":[{"award-number":["U01\u2010AG6057195"]}],"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":["R56\u2010AG057195"],"award-info":[{"award-number":["R56\u2010AG057195"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["AARG\u201022\u2010926940"],"award-info":[{"award-number":["AARG\u201022\u2010926940"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["LDRFP\u201021\u2010818464"],"award-info":[{"award-number":["LDRFP\u201021\u2010818464"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["LEADS GENETICS\u201019"],"award-info":[{"award-number":["LEADS GENETICS\u201019"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2025,8]]},"abstract":"\n Objective<\/jats:title>\n Early\u2010onset Alzheimer's disease (EOAD) and late\u2010onset Alzheimer's disease (LOAD) differ in many respects. Here, we address the issue of possible differences in fibrillar amyloid pathology as measured by positron emission tomography (PET), which remains unresolved due to the lack of large\u2010scale comparative studies.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Three hundred ninety\u2010nine cognitively impaired participants younger than 65\u2009years of age from the multicenter Longitudinal Early\u2010onset Alzheimer's Disease Study (LEADS) and 450 cognitively impaired participants older than 65\u2009years from the Alzheimer's Disease Neuroimaging Initiative (ADNI) underwent clinical assessment, brain magnetic resonance imaging (MRI), and amyloid PET and were included in this study. We compared amyloid PET outcomes (positivity rate based on visual read and quantified tracer uptake expressed as Centiloids [CLs]) between the 2 cohorts and studied their association with age, sex,\n APOE<\/jats:italic>\n genotype, and cognition.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The amyloid positivity rate was higher in LEADS (78%, 95% confidence interval [CI]\u2009=\u200974\u201382) than in ADNI (71%, 95% CI\u2009=\u200967\u201375,\n p<\/jats:italic>\n \u2009=\u20090.02). Lower Mini\u2010Mental State Examination (MMSE) and APOE4 genotype increased the odds of amyloid positivity in both cohorts. Visually positive scans had higher CLs in LEADS (EOAD, mean\u2009=\u200995.3\u2009\u00b1\u200926.1) than in ADNI (LOAD, mean\u2009=\u200980.9\u2009\u00b1\u200936.8,\n p<\/jats:italic>\n \u2009<\u20090.0001), predominantly in parietal cortex\/precuneus, superior temporal, and frontal cortices. In amyloid\u2010positive patients, (1) CLs were higher in female patients in both cohorts; (2) APOE4 carriership was associated with\n lower<\/jats:italic>\n CLs in EOAD, which was not observed in LOAD; and (3) correlations between CLs and MMSE scores were significantly stronger in EOAD than in LOAD.\n <\/jats:p>\n <\/jats:sec>\n \n Interpretation<\/jats:title>\n Differences in the burden of amyloid pathology may contribute to differences in clinical and anatomic patterns in sporadic EOAD and LOAD, and have implications for optimizing therapeutic strategies in each group. ANN NEUROL 2025;98:236\u2013248<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/ana.27233","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T05:01:26Z","timestamp":1742187686000},"page":"236-248","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Amyloid\n PET<\/scp>\n in Sporadic Early\u2010 Versus Late\u2010Onset Alzheimer's Disease: Comparison of the\n LEADS<\/scp>\n and\n ADNI<\/scp>\n Cohorts"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2018-261X","authenticated-orcid":false,"given":"Julien","family":"Lagarde","sequence":"first","affiliation":[{"name":"Department of Neurology University of California, San Francisco San Francisco CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piyush","family":"Maiti","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California, San Francisco San 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