ArticleBrain, behavior, & immunity - health2026
Intersectional effects of race/ethnicity, sex, and APOE4 on plasma inflammatory profiles in Hispanic and non-Hispanic white adults.
Article in Brain, behavior, & immunity - health, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Despite known links between inflammation and Alzheimer's disease (AD), little is understood about how inflammatory processes vary across racial/ethnic and sex groups, particularly in relation to the major genetic risk factor apolipoprotein E ε4 (APOE4), whether these differences contribute to AD disparities among understudied Hispanics. Objective: This study investigated the interactive effects of race/ethnicity, sex, and APOE4 status on plasma inflammatory markers (IL-5, IL-6, IL-10, TNF-α). Secondary analyses examined whether these inflammatory markers were associated with cognitive performance and plasma AD-related biomarkers. Methods: Cross-sectional baseline data from the Health & Aging Brain Study - Health Disparities (HABS-HD) were analyzed in a multiethnic cohort of 1348 non-Hispanic white (NHW) (56.9% women, 27.4% APOE4 carriers) and 1420 Hispanics (66% women, 17.6% APOE4 carriers). Linear regression models examined main and interaction effects between race/ethnicity, sex, and APOE4 on plasma inflammatory markers, adjusting for age, education, BMI, and vascular comorbidities. Follow-up models tested associations with plasma AD biomarkers (Aβ42/40, pTau181) and cognition. Results: Significant three-way interactions were observed for IL-10 (p = 0.012) and at trend-level for IL-5 (p = 0.056), with the highest inflammatory levels in Hispanic men who are APOE4 carriers. No consistent associations emerged between inflammatory markers and global cognition or plasma AD biomarkers. An IL-10 × race/ethnicity interaction was associated with language performance (p = 0.035), though this did not survive correction for multiple comparisons. Conclusion: Inflammatory responses to APOE4 differ by race/ethnicity and sex, with Hispanic men showing elevated IL-10 and IL-5. While associations with cognition and AD biomarkers were limited, these findings highlight intersectional heterogeneity in inflammatory profiles that may contribute to understanding biological pathways underlying AD disparities. Longitudinal studies are needed to determine whether these cytokines predict future cognitive decline or AD pathology.
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