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In this validation study, we quantified amyloid-beta (A\u03b2) deposits, evaluating multiple brain regions across institutions, and evaluated associations with clinical, demographic, and genetic factors in persons pathologically diagnosed with AD. All linear models were adjusted for sex, age of death, ethnicity, and center. We analyzed densities (#\/mm2) of cored plaques, diffuse plaques, and cerebral amyloid angiopathy (CAA) in 273 individuals from 3 Alzheimer\u2019s Disease Research Centers. Formalin-fixed paraffin-embedded sections of frontal, temporal, and parietal cortices were immunostained and digitized, generating 799 whole-slide images (WSIs). Following log transformation, mixed-effects modeling revealed the parietal cortex had the highest cored plaque densities (P\u2009&amp;lt;\u2009.001); the temporal cortex had the highest diffuse plaque (P\u2009&amp;lt;\u2009.001); CAA showed no regional differences. Wilcoxon rank-sum test, and covariates adjusted linear models showed ApoE \u03b54\u2212 status was associated with higher cored plaque densities in the temporal lobe (P\u2009=\u2009.04). ApoE \u03b54+ status was associated with diffuse plaques in the temporal lobe (P\u2009=\u2009.001), and CAA in the frontal lobe (P\u2009=\u2009.004). These findings provide further validation and provide exploratory associations advancing deeper phenotyping of AD.<\/jats:p>","DOI":"10.1093\/jnen\/nlaf152","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T12:59:56Z","timestamp":1764680396000},"page":"537-550","source":"Crossref","is-referenced-by-count":2,"title":["Clinical and pathologic correlations of machine learning quantification of A\u03b2 deposits across 3 brain regions of decedents with Alzheimer disease"],"prefix":"10.1093","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4021-1927","authenticated-orcid":false,"given":"David","family":"Garcia","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California, Davis , Sacramento, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8550-8443","authenticated-orcid":false,"given":"Shivam Rajendra","family":"Rai Sharma","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California, Davis , Sacramento, CA,","place":["United States"]},{"name":"Department of Computer Science, University of California, Davis , Davis, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, University of California, Davis , Davis, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurel","family":"Beckett","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, University of California, Davis , Davis, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise Nicole C","family":"Sevilla","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California, Davis , Sacramento, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"La Rissa","family":"Vasquez","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California, Davis , Sacramento, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles S","family":"DeCarli","sequence":"additional","affiliation":[{"name":"Department of Neurology, Alzheimer\u2019s Disease Research Center, University of California, Davis, School of Medicine , Sacramento, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Gutman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Emory University School of Medicine , Atlanta, GA,","place":["United States"]},{"name":"Department of Psychiatry, Emory University School of Medicine , Atlanta, GA,","place":["United States"]},{"name":"Department of Biomedical Informatics, Emory University School of Medicine , Atlanta, GA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Vizcarra","sequence":"additional","affiliation":[{"name":"Department of Neurology, Emory University School of Medicine , Atlanta, GA,","place":["United States"]},{"name":"Department of Psychiatry, Emory University School of Medicine , Atlanta, GA,","place":["United States"]},{"name":"Department of Biomedical Informatics, Emory University School of Medicine , Atlanta, GA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G","family":"Coughlin","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, San Diego , La Jolla, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew F","family":"Teich","sequence":"additional","affiliation":[{"name":"Department of Neurology, Taub Institute for Research on Alzheimer\u2019s Disease and Aging Brain, Columbia University Medical Center , New York, NY,","place":["United States"]},{"name":"Department of Pathology and Cell Biology, Columbia University Medical Center , New York, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, University of California, Davis , Davis, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan M","family":"Mungas","sequence":"additional","affiliation":[{"name":"Department of Neurology, Alzheimer\u2019s Disease Research Center, University of California, Davis, School of Medicine , Sacramento, CA,","place":["United 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