What does this research mean for the field?

The impact of the ApoE ε4 allele on hippocampal volume, episodic memory, and Alzheimer's clinical syndrome varies significantly by ethnoracial group, with the strongest effects observed in White individuals compared to Black/African American and Hispanic/Latino individuals. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

What question did this study set out to answer?

To assess how the ApoE4 genotype affects cognitive performance and brain structure across different ethnoracial groups.

March 21, 2026Open Access

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

Key Points

To assess how the ApoE4 genotype affects cognitive performance and brain structure across different ethnoracial groups.
Analyzed data from 946 participants with ApoE genotype and magnetic resonance imaging scans.
Utilized regression and structural equation modeling to test effects on cognition.
Examined variation in effects across ethnoracial groups: White, Black/African American, and Hispanic/Latino.
ApoE4 was associated with higher clinical syndrome prevalence (odds ratio = 3.0).
Lower hippocampal volume correlated with the ApoE4 genotype (ß = -0.14).
Weaker memory performance was noted in ApoE4 carriers compared to non-carriers (ß = -0.21).
The indirect effect of ApoE4 on cognition was most pronounced in White participants.

Abstract

Abstract INTRODUCTION 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. METHODS 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. RESULTS 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. DISCUSSION 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.

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

Key Points

Abstract

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