Faculty, Staff and Student Publications

Language

English

Publication Date

3-1-2026

Journal

Alzheimer's & Dementia

DOI

10.1002/alz.71213

PMID

41816965

PMCID

PMC13093554

PubMedCentral® Posted Date

3-12-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Apolipoprotein E (APOE) alleles are well-established genetic risk factors for Alzheimer's disease (AD), but their effects on AD biomarkers (amyloid beta [Aβ]42/40, phosphorylated tau [p-tau]181, neurofilament light chain [NfL], and glial fibrillary acidic protein [GFAP]) may vary across populations due to ancestry-, age-, and sex-related differences. We hypothesized that these effects vary across Hispanic/Latino background groups with distinct ancestral admixture.

Methods: We analyzed ε2 and ε4 allele associations with AD biomarkers using survey-weighted linear regression models, adjusting for demographic covariates. Secondary analyses examined genetic analysis group- and ancestry-specific effects.

Results: ε4 was associated with lower Aβ42/40 and higher p-tau181and GFAP levels, but not with NfL, suggesting its role in Aβ and tau deposition and neuroinflammation. ε4 associations were stronger in those with higher European and lower African ancestry.

Discussion: These findings expand on prior studies suggesting that genetic ancestry modifies APOE-associated AD risk in Hispanic/Latino populations and highlight the importance of capturing ancestry-based heterogeneity in AD biomarker research.

Keywords

Aged, Aged, 80 and over, Female, Humans, Male, African People, Alzheimer Disease, Amyloid beta-Peptides, Apolipoprotein E4, Apolipoproteins E, Biomarkers, Glial Fibrillary Acidic Protein, Hispanic or Latino, Neurofilament Proteins, Peptide Fragments, tau Proteins, White, Alzheimer's disease, amyloid/tau/neurodegeneration framework, apolipoprotein E, genetic ancestry, Hispanics/Latinos, plasma biomarkers

Published Open-Access

yes

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