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A subsample had longitudinal assessment and plasma p\u2010tau. We tested the modifying effects of global and local ancestries. Results were replicated in an independent Peruvian cohort and brain samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p><jats:italic>APOE<\/jats:italic> \u03b54 effect was strongest in Peruvians\/Bolivians (odds ratio [OR]\u00a0=\u00a06.13, 95% confidence interval [CI]\u00a0=\u00a02.71\u201313.83), followed by Mexicans (OR\u00a0=\u00a04.31, 95% CI\u00a0=\u00a01.58\u201311.74), Mexican\u2010Americans (OR\u00a0=\u00a03.06, 95% CI\u00a0=\u00a02.04\u20134.59), and Caribbean\u2010Hispanics (OR\u00a0=\u00a02.22, 95% CI\u00a0=\u00a01.99\u20132.48). Meta\u2010analyses showed OR\u00a0=\u00a02.32 (95% CI\u00a0=\u00a02.09\u20132.57) and OR\u00a0=\u00a00.81 (95% CI\u00a0=\u00a00.68\u20130.97) for the \u03b54 and \u03b52 allele, respectively. The <jats:italic>APOE<\/jats:italic> \u03b54 effect was replicated independently in Peruvians (OR\u00a0=\u00a05.06, 95% CI\u00a0=\u00a02.48\u201310.70). \u03b54 carriers displayed higher ADRD conversions and p\u2010tau levels. Global and local ancestries did not modify ADRD risk, and they were associated with Braak stage.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p><jats:italic>APOE<\/jats:italic> shows a heterogeneous effect on ADRD risk in our Hispanics\/Latinos sample, the largest to date.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>The apolipoprotein E (<jats:italic>APOE<\/jats:italic>) \u03b54 effect is stronger in Peruvians\/Bolivians than in other Hispanic\/Latino groups.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The strong <jats:italic>APOE<\/jats:italic> effect size in Peruvians and Bolivians was replicated in a second independent Peruvian cohort.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Meta\u2010analysis for \u03b54 and \u03b52 confirmed a significant association with Alzheimer's disease and related dementias (ADRD).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Global and local ancestry do not modify the association between <jats:italic>APOE<\/jats:italic> genotype and ADRD.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.70138","type":"journal-article","created":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T06:06:26Z","timestamp":1744437986000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["<i>APOE<\/i> and Alzheimer's disease and related dementias risk among 12,221 Hispanics\/Latinos"],"prefix":"10.1002","volume":"21","author":[{"given":"Sandra","family":"Barral","sequence":"first","affiliation":[{"name":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons Columbia University  New York New York USA"},{"name":"The Gertrude H. 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