Impact of Ethnicity on the Utility of Plasma Amyloid and Tau to Predict Alzheimer's Disease

ABSTRACT The development of biomarkers for Alzheimer’s disease resulted in the use of positron emission tomography (PET) and biofluid assays to detect AD pathology before clinical symptoms. However, these studies were conducted in predominantly non-Hispanic white populations to establish cut-off values for clinical trial recruitment, which have not translated well to Hispanic and African Americans (AA). The proposed project aims to comprehensively measure phosphorylated tau species p-tau217 in plasma from the Health and Aging Brain Study-Health Disparities (HABS-HD) study. We have previously demonstrated that combining p-tau217 with Aβ42/40 ratio and other AD covariates into predictive models resulted in detecting amyloid positivity at ≥ 20 Centiloids with 88% sensitivity and 90% specificity. We propose to leverage the HABS-HD cohort plasma samples to quantify plasma Aβ42/40 and p-tau217 levels in amyloid PET positive and negative in Hispanic and AA populations to determine cutoffs relevant to ethnicity and race. The overarching hypothesis of this project is that plasma biomarkers related to AD pathology present differently among diverse populations and as a result have different relations to established clinical outcomes such as PET amyloid levels and cognitive outcomes. To test this hypothesis, we propose to characterize plasma p-tau217 and Aβ42/40 in Mexican Americans, AA and non-Hispanic white populations of the HABS-HD study. Additionally, we propose to investigate how other AD hallmarks are associated with p-tau217 and Aβ42/40 in these individual populations. Resultant data will not only document the biomarker protein levels for the HABS-HD cohort for sharing in the longitudinal study but may also inform on whether amyloid PET scans can be reduced in the screening process.