Faculty, Staff and Student Publications

Language

English

Publication Date

4-1-2025

Journal

Alzheimer's & Dementia

DOI

10.1002/alz.70138

PMID

40219824

PMCID

PMC11992591

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.

Keywords

Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Alzheimer Disease, Apolipoprotein E4, Apolipoproteins E, Cohort Studies, Dementia, Genetic Predisposition to Disease, Genotype, Hispanic or Latino, Longitudinal Studies, Peru, Risk Factors, tau Proteins, South American People, admixture, ADRD, APOE, health disparities, Hispanic/Latino population

Published Open-Access

yes

Download

Included in

Public Health Commons

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.