Generalizability of Tau and Amyloid Plasma Biomarkers in Alzheimer's Disease Cohorts of Diverse Genetic Ancestries

Introduction: Plasma phosphorylated threonine-181 of Tau and amyloid beta are biomarkers for differential diagnosis and preclinical detection of Alzheimer disease (AD). Given differences in AD risk across diverse populations, generalizability of existing biomarker data is not assured.

Methods: In 2,086 individuals of diverse genetic ancestries (African American, Caribbean Hispanic, and Peruvians) we measured plasma pTau-181 and Aβ42/Aβ40. Differences in biomarkers between cohorts and clinical diagnosis groups and the potential discriminative performance of the two biomarkers were assessed.

Results: pTau-181 and Aβ42/Aβ40 were consistent across cohorts. Higher levels of pTau181 were associated with AD while Aβ42/Aβ40 had minimal differences. Correspondingly, pTau-181 had greater predictive value than Aβ42/Aβ40, however, the area under the curve differed between cohorts.

Discussion: pTau-181 as a plasma biomarker for clinical AD is generalizable across genetic ancestries, but predictive value may differ. Combining genomic and biomarker data from diverse individuals will increase understanding of genetic risk and refine clinical diagnoses.