Abstract
INTRODUCTION: Factors influencing plasma Alzheimer's disease (AD) biomarkers remain incompletely understood. Here we evaluated Fujirebio plasma p-Tau(217) in two diverse cohorts among whom 91% underwent cerebrospinal fluid (CSF) analysis. METHODS: Non-Hispanic White (NHW, n = 113), Black/African American (B/AA, n = 66), and Chinese American (ChA, n = 38) participants recruited from two universities were included. We examined if plasma p-Tau(217) correlated with CSF and clinical factors, differed between racial groups, and associated with novel CSF proteins. RESULTS: CSF p-Tau(181) strongly correlated with CSF p-Tau(217) (R(2 )= 0.912) which moderately correlated with plasma p-Tau(217) (R(2 )= 0.694). Plasma p-Tau(217) levels were higher with greater cognitive impairment but lower in B/AA than NHW participants even after adjusting for CSF p-Tau(181). This resulted in greater positive predictive value for NHW than B/AA participants, and could be mediated by complement or lysosomal pathways. DISCUSSION: Severity of cognitive impairment and race both influence plasma p-Tau(217) levels beyond race-associated differences in CSF p-Tau(181). HIGHLIGHTS: Cognitive impairment associates with plasma p-Tau(217) independent of CSF biomarkers. Black/African Americans had lower plasma p-Tau(217) than non-Hispanic White Americans. CSF p-Tau(181) could not explain lower plasma p-Tau(217) in Black/African Americans. Plasma p-Tau(217) difference results in more false positive cases according to race. Novel CSF processes were associated with race-related plasma p-Tau(217) difference.