Association of apolipoprotein E genotype with cognitive performance: findings from the University of California, Davis Alzheimer's Disease Research Center longitudinal diversity cohort.

Authors

Eva Min, Brandon Gavett, Shraddha Sapkota, Sarah Tomaszewski Farias, David Johnson, Lee-Way Jin, Pauline Maillard, Evan Fletcher, Rachel A Whitmer, Charles DeCarli

Published in

Alzheimer's & dementia (Amsterdam, Netherlands). Volume 18. Issue 1. Pages e70304. Epub Mar 19, 2026.

Abstract

The apolipoprotein E (ApoE) ε4 allele is a key genetic risk for Alzheimer's disease, but its effects may differ by heritage. We examined how ApoE4 influences hippocampal volume, episodic memory, and clinical syndrome across race and ethnicity (ethnoracial) groups.
We analyzed 946 participants with the ApoE genotype, clinical diagnosis, and magnetic resonance imaging scans. Regression and structural equation modeling tested ApoE4's impact on cognition and whether an ethnoracial group consisting of 486 White, 234 Black/African American, or 226 Hispanic/Latino individuals moderated these effects.
ApoE4 prevalence increased with the clinical syndrome (odds ratio [OR] = 3.0, p < 0.0001). It correlated with lower hippocampal volume (ß = -0.14, p < 0.001) and weaker memory performance (ß = -0.21, p < 0.001). The indirect effect of ApoE4 via hippocampal volume was largest among White participants.
ApoE4's influence on hippocampal volume, episodic memory and clinical syndrome varies by ethnoracial group, with the strongest effects among White individuals. Our findings necessitate further AD biomarker research, as standard markers may not apply universally.

PMID:
42840901
Bibliographic data and abstract were imported from PubMed on 07 Oct 2026.

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