Sociodemographic and comorbidity factors mediate ethno-racial differences in plasma Alzheimer’s disease biomarkers

Ethno-racial disparities in Alzheimer's disease (AD) risk are well-documented, yet mechanisms underlying these differences remain poorly understood. This study investigates plasma AD biomarkers reflective of amyloid, tau, neurodegeneration, and inflammation across Hispanic, non-Hispanic Black/ African American, and non-Hispanic White adults, and examines whether social determinants of health (SDOH) and comorbidities mediate observed disparities. Data from the community-based Health and Aging Brain Study – Health Disparities (HABS-HD) included 1,256 Hispanic, 723 Black, and 1,243 non-Hispanic White participants. Group differences in plasma biomarkers (phosphorylated tau-217 [p-tau217], amyloid-β 42/40 ratio [Aβ42/40], phosphorylated tau-181 [p-tau181], total tau, neurofilament light chain [NfL], and glial fibrillary acidic protein [GFAP]) were assessed using ANCOVA adjusted for age, sex, APOE-ε4 status, and cognitive status. Multiple mediation models tested whether social determinants of health (income, education, area deprivation, chronic stress, social support) and comorbidity factors (BMI, creatinine, total cholesterol, HbA1c, systolic blood pressure) mediate group differences, with covariates and mediators considered simultaneously, resulting in 22 mediation models. Significant differences were observed across all plasma biomarkers. Both Black and Hispanic adults showed lower p-tau217 and p-tau181 compared to non-Hispanic White adults ( p 's < 0.001). Hispanic adults exhibited lower Aβ42/40 compared to both groups ( p 's < 0.05) and lower GFAP compared to non-Hispanic White adults ( p = 0.002), but higher total tau ( p 's < 0.01) compared to both groups. Hispanics had higher NfL than Black adults ( p < 0.001) but did not differ from non-Hispanic Whites, while Black adults had lower NfL than non-Hispanic White adults ( p < 0.001). Comorbidity factors, particularly creatinine (10 of 22 models), BMI (8 models), and HbA1c (7 models), consistently mediated biomarker differences. SDOH factors demonstrated mediation for Aβ42/40, p-tau181, and NfL, with area deprivation and education as key mediators. SDOH and comorbidities were associated with plasma AD biomarker differences observed across ethno-racial groups, though their influence varies by biomarker type and comparison group. Renal function (creatinine), metabolic factors (BMI, HbA1c), and structural disadvantages (area deprivation, education) emerged as critical factors. However, many effects remain unexplained, suggesting additional biological, environmental, or unmeasured social factors contribute to disparities. These findings highlight the need for precision medicine approaches that integrate biological, systemic health, and social contexts when interpreting biomarkers and guiding dementia prevention.