The effect of APOE4 on Alzheimer's plasma biomarkers among Mexican Americans in the HABS-HD cohort.

Background and objectives: The relationship between APOE4 status and plasma biomarkers previously shown to be related to Alzheimer's risk have not been carefully examined among Mexican Americans. This research is needed to elucidate disparities within the Alzheimer's field by evaluating key genetic factors in an underrepresented population. The present study deepens our understanding of the interaction between biological and genetic factors for these populations with greater incidence of Alzheimer's disease (AD) and helps address whether APOE4 confers similar risk of AD in Mexican Americans as previously reported in Non-Hispanic Whites.

Methods: Cross-sectional data consisting of 792 Mexican American and 785 Non-Hispanic White participants from the Health & Aging Brain Study - Health Disparities (HABS-HD) with available plasma biomarkers and APOE4 genotype profiles were included in the present study. Linear regression models were used to test our hypotheses. APOE4-Race/ethnicity interaction term tested whether the biomarker levels differed between ethnic groups. Analyses were adjusted for age, gender, and education. Further analyses explored whether biomarker levels differed by APOE4 carrier status within racial/ethnic groups.

Results: Among 1577 participants (59.5% women; mean age 66.4 ± 8.74 years), significant differences were observed across race/ethnic and APOE4 groups. Mexican Americans were younger (p < 0.001), had a higher proportion of women (p = 0.001), fewer years of education (p < 0.001), and lower MMSE scores (p < 0.001). Biomarker differences between Mexican Americans and Non-Hispanic Whites included variations in Aβ42/Aβ40 (p = 0.03) and p-tau181 (p < 0.001), but not in total tau, TNF-α, or NfL levels (all p > 0.12). Race/ethnicity-APOE4 interactions were significant for Aβ42/Αβ40, p-tau181, and total tau (all p < 0.05) but not for NfL or TNF-α. APOE4 associations with Aβ42/Aβ40 and p-tau181 were significant in NH White participants (all p < 0.001) but not among Mexican Americans.

Conclusion: These findings will significantly contribute to understanding potential differences in the role of APOE4 and AD plasma biomarkers among Mexican Americans. This research has the potential to enhance preventive care and early diagnosis for populations with a higher incidence of AD.