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Interaction between Residential Segregation and Genetic Susceptibility to Alzheimer’s Disease Among Racially and Ethnically Diverse Older Adults

Poster Session C - Sunday, March 8, 2026, 5:00 – 7:00 pm PDT, Fairview/Kitsilano Ballrooms

Yemi L. Tchala¹, Abbey M. Hamlin¹, Vincent T. Holm¹, Christian J. Jackson¹, Alexandra L. Clark¹; ¹University of Texas at Austin

Introduction: Residential segregation is an important environmental determinant of health that shapes exposure to harmful risk factors (e.g., stress, pollution). Segregation has been associated with poor late-life cognitive health, and biopsychosocial models suggest its adverse effects may be amplified among individuals with genetic susceptibility to Alzheimer’s disease (AD). This study examined whether apolipoprotein (APOE) ε4 moderated the association between segregation and AD risk in a large, racially/ethnically diverse sample. Methods: 113 community-dwelling older adults (Mean age = 65; 61% Black/Latino) completed MRI scans, blood draws, and cognitive testing. Baseline residential addresses were geocoded and linked with 2020 U.S. census data to estimate current segregation levels using the interaction index. APOE-ε4 status was determined by the presence of at least one ε4 allele. AD risk-related outcomes included plasma amyloid-beta 42:40 (Aβ42:40), quantified via immunoassays, and hippocampal volumes estimated using HippoDeep. Analyses utilized generalized estimation equations (GEE), accounting for age, sex, race/ethnicity, geographic clustering, and intracranial volume (hippocampal volume only). Results: GEE models revealed a significant segregation x APOE-ε4 status moderation effect on plasma Aβ42:40 (B=-0.70, p=.001). Higher segregation was associated with worse AD pathology (B=-0.44, p= .011) among APOE-ε4 carriers, but there was no association in non-carriers. There was a significant segregation x APOE-ε4 effect for left (B=-0.41, p=.035), but not right hippocampal volume (B=-0.24, p=.252). Higher segregation was linked to lower hippocampal volume among APOE-ε4 carriers (B =-0.26, p =.076). Conclusion: Findings suggest that gene x environment interactions play an important role in shaping biological risk for AD.

Topic Area: LONG-TERM MEMORY: Development & aging