Influence of cognitive impairment and race on plasma p-Tau217 in two diverse cohorts

Abstract

INTRODUCTION

Factors influencing plasma Alzheimer's disease (AD) biomarkers remain incompletely understood. Here we evaluated Fujirebio plasma p-Tau₂₁₇ 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-Tau₂₁₇ correlated with CSF and clinical factors, differed between racial groups, and associated with novel CSF proteins.

RESULTS

CSF p-Tau₁₈₁ strongly correlated with CSF p-Tau₂₁₇ (R² = 0.912) which moderately correlated with plasma p-Tau₂₁₇ (R² = 0.694). Plasma p-Tau₂₁₇ levels were higher with greater cognitive impairment but lower in B/AA than NHW participants even after adjusting for CSF p-Tau₁₈₁. 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-Tau₂₁₇ levels beyond race-associated differences in CSF p-Tau₁₈₁.

Highlights

• Cognitive impairment associates with plasma p-Tau₂₁₇ independent of CSF biomarkers.
• Black/African Americans had lower plasma p-Tau₂₁₇ than non-Hispanic White Americans.
• CSF p-Tau₁₈₁ could not explain lower plasma p-Tau₂₁₇ in Black/African Americans.
• Plasma p-Tau₂₁₇ difference results in more false positive cases according to race.
• Novel CSF processes were associated with race-related plasma p-Tau₂₁₇ difference.