{"doi":"10.1002/alz.70138","title":"<i>APOE</i> and Alzheimer's disease and related dementias risk among 12,221 Hispanics/Latinos","abstract":"BACKGROUND: Effect of apolipoprotein E (APOE) on Alzheimer's disease and related dementias (ADRD) risk is heterogeneous across populations, with scarce data on Hispanics/Latinos. METHODS: APOE genotype was studied in 12,221 Hispanics/Latinos (per cohort and via metanalysis): Caribbean-Hispanics, Mexicans, Mexican-Americans, and Peruvians/Bolivians. A subsample had longitudinal assessment and plasma p-tau. We tested the modifying effects of global and local ancestries. Results were replicated in an independent Peruvian cohort and brain samples. RESULTS: APOE ε4 effect was strongest in Peruvians/Bolivians (odds ratio [OR] = 6.13, 95% confidence interval [CI] = 2.71-13.83), followed by Mexicans (OR = 4.31, 95% CI = 1.58-11.74), Mexican-Americans (OR = 3.06, 95% CI = 2.04-4.59), and Caribbean-Hispanics (OR = 2.22, 95% CI = 1.99-2.48). Meta-analyses showed OR = 2.32 (95% CI = 2.09-2.57) and OR = 0.81 (95% CI = 0.68-0.97) for the ε4 and ε2 allele, respectively. The APOE ε4 effect was replicated independently in Peruvians (OR = 5.06, 95% CI = 2.48-10.70). ε4 carriers displayed higher ADRD conversions and p-tau levels. Global and local ancestries did not modify ADRD risk, and they were associated with Braak stage. DISCUSSION: APOE shows a heterogeneous effect on ADRD risk in our Hispanics/Latinos sample, the largest to date. HIGHLIGHTS: The apolipoprotein E (APOE) ε4 effect is stronger in Peruvians/Bolivians than in other Hispanic/Latino groups. The strong APOE effect size in Peruvians and Bolivians was replicated in a second independent Peruvian cohort. Meta-analysis for ε4 and ε2 confirmed a significant association with Alzheimer's disease and related dementias (ADRD). Global and local ancestry do not modify the association between APOE genotype and ADRD.","journal":"Alzheimer s & Dementia","year":2025,"id":513760,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9339,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1077988,"name":"Zikun Yang","orcid":"0000-0002-8834-6377","position":1,"is_corresponding":false},{"id":432398,"name":"Nicole Phillips","orcid":"0000-0002-9324-2687","position":2,"is_corresponding":false},{"id":440139,"name":"Robert C. 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Jiménez Velázquez","orcid":null,"position":19,"is_corresponding":false},{"id":803747,"name":"Victoria Marca","orcid":null,"position":20,"is_corresponding":false},{"id":501454,"name":"Maryenela Illanes‐Manrique","orcid":"0000-0002-3098-0981","position":21,"is_corresponding":false},{"id":432533,"name":"Mario Cornejo‐Olivas","orcid":"0000-0001-6313-5680","position":22,"is_corresponding":false},{"id":6903,"name":"Margaret A. Pericak‐Vance","orcid":"0000-0001-7283-8804","position":23,"is_corresponding":false},{"id":336045,"name":"Rebeca Wong","orcid":"0000-0001-7287-0660","position":24,"is_corresponding":false},{"id":270462,"name":"Sid E. 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