{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:25:54Z","timestamp":1793060754490,"version":"4.5.0"},"reference-count":55,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:sec id=\"ab-noi260002-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Sex and racial or ancestral disparities in Alzheimer disease remain incompletely understood; autopsy studies that examine amyloid, tau, and genetic factors are scarce.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi260002-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To test whether neuritic plaque burden and cognitive outcomes differ by sex and whether sex modifies the effects of apolipoprotein E \u03b54 (\n                      <jats:italic toggle=\"yes\">APOE\u03b54<\/jats:italic>\n                      ), informant-reported race, and African ancestry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi260002-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>This was a cross-sectional study using postmortem neuropathological data from the Biobank for Aging Studies, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil. A total of 2268 autopsies from a population-based, diverse clinicopathological sample were collected between April  2004 and March 2025.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi260002-7\">\n                    <jats:title>Exposures<\/jats:title>\n                    <jats:p>\n                      Sex, informant-reported race (Black, White), African ancestry proportion, and\n                      <jats:italic toggle=\"yes\">APOE\u03b54<\/jats:italic>\n                      carrier status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi260002-8\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>\n                      Neuritic plaque burden (Consortium to Establish a Registry for Alzheimer\u2019s Disease [CERAD] score), and cognitive function (Clinical Dementia Rating\u2013Sum of Boxes [CDR-SB]). Ordinal logistic regression examined association of sex with CERAD scores and 2- and 3-way interactions among sex, race, ancestry, and\n                      <jats:italic toggle=\"yes\">APOE\u03b54<\/jats:italic>\n                      ; adjusting for age, education, vascular factors, and Braak stages. Linear models related pathology to CDR-SB, adding copathologies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi260002-9\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The analysis included 2268 autopsies (median [IQR] age, 74.8 [63.8-83.3] years; 1152 [51% male] and 1116 [49%] female; 802 [35%] Black and 1466 [65%] White; other race groups not included owing to small numbers); female individuals were older than male individuals and more likely to exhibit cognitive impairment (CDR global score \u22650.5). Female individuals had higher plaque burden than male individuals (unadjusted odds ratio [OR], 1.97; 95% CI, 1.67-2.29;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001), and this association remained significant in adjusted models for sociodemographic and vascular factors and\n                      <jats:italic toggle=\"yes\">APOE\u03b54<\/jats:italic>\n                      status (adjusted OR, 1.65; 95% CI, 1.33-2.20;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001).\n                      <jats:italic toggle=\"yes\">APOE\u03b54<\/jats:italic>\n                      carriers of both sexes had an approximately 4-fold greater odds of plaques. Significant 2-way interactions were found between sex,\n                      <jats:italic toggle=\"yes\">APOE\u03b54<\/jats:italic>\n                      status, race, and ancestry on CERAD scores. Black noncarriers (OR, 0.47; 95% CI, 0.34-0.67) and noncarriers of African ancestry (OR, 0.57; 95% CI, 0.43-0.76) were least likely to have high plaque burden, whereas this protection was weakened in \u03b54 carriers. No significant 3-way interaction was detected. Among individuals with a CERAD score of 2 or higher, female individuals were more likely than male individuals to reach Braak stage V-VI than male individuals (probability ratio, 1.25; 95% CI, 1.13-1.38;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.002). Adding Braak stage to multivariable models attenuated the female-male difference in plaques and interaction of sex and plaque on CDR-SB was no longer significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi260002-10\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>\n                      The findings indicate that female sex,\n                      <jats:italic toggle=\"yes\">APOE\u03b54<\/jats:italic>\n                      , and both race and African ancestry were jointly associated with amyloid in this study population. Excess amyloid among women may partly explain their greater tau burden and steeper cognitive decline. These findings highlight the importance of incorporating sex, race, and ancestry into biomarker thresholds, risk stratification, and the design of preventive or disease-modifying trials for Alzheimer disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamaneurol.2026.0054","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T16:30:34Z","timestamp":1771864234000},"page":"392","source":"Crossref","is-referenced-by-count":11,"title":["Sex Differences in Amyloid Pathology by Race, Ancestry, and Apolipoprotein E \u03b54 in an Admixed Autopsy Sample"],"prefix":"10.1001","volume":"83","author":[{"given":"Maison","family":"Abu Raya","sequence":"first","affiliation":[{"name":"Global Brain Health Institute, University of California, San Francisco"},{"name":"Memory and Aging Center, University of California, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia 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