Journal Article

APOE and Alzheimer's disease and related dementias risk among 12,221 Hispanics/Latinos

Tosto, Giuseppe, Obregon, Alejandra Michaels, Cieza, Basilio, Cuccaro, Michael L., Arango, Silvia Mejia, Montesinos, Rosa, Custodio, Nilton, Yang, Zikun, Brickman, Adam M., Velazquez, Ivonne Z. Jimenez, Marca, Victoria, Phillips, Nicole, Vance, Jeffery M., Illanes‐Manrique, Maryenela, Rajabli, Farid, Mayeux, Richard, Pericak‐Vance, Margaret, Wong, Rebeca, Barber, Robert C., Duran, Juan Carlos, Cusicanqui, Maria, Samper‐Ternent, Rafael, Reyes‐Dumeyer, Dolly, O'Bryant, Sid, Honig, Lawrence S., Barral, Sandra, Cornejo‐Olivas, Mario, Soto‐Añari, Marcio

2025

Overview

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.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: admixture / ADRD / African Americans / Aged / Aged, 80 and over / Aging / Alzheimer Disease - ethnology / Alzheimer Disease - genetics / Alzheimer's disease / Antibodies / APOE / Apolipoprotein E4 - genetics / Apolipoproteins / Apolipoproteins E - genetics / Biomarkers / Brain / Cohort Studies / Consortia / Dementia / Dementia - genetics / Disease / Female / Gene loci / Genetic Predisposition to Disease / Genotype / Genotype & phenotype / Genotypes / Global local relationship / health disparities / Health risk assessment / Heterogeneity / Hispanic Americans / Hispanic or Latino - genetics / Hispanic/Latino population / Humans / Latin American cultural groups / Longitudinal Studies / Male / Meta-analysis / Mexican Americans / Middle Aged / Neuropsychology / Peru / Risk / Risk Factors / South American People - genetics / tau Proteins - blood