Abstract Details

Title Influence of Cognitive Impairment and Race on Plasma P-Tau217 in Two Diverse Cohorts

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) S15 - Innovations in Alzheimer's Diagnostics (2:00 PM-2:12 PM)

Poster/Presentation
Number 006

Background Factors influencing plasma AD biomarkers remain incompletely understood, in part due to correlative studies involving plasma biomarkers and cerebral PET imaging omitting CSF biomarker analysis. This is particularly important as we and others previously identified Black/African American (B/AA) adults to have lower CSF p-Tau levels than non-Hispanic White (NHW) adults. Here we evaluated the relationship between CSF p-Tau₂₁₇ and CSF p-Tau₁₈₁, as well as their relationships to plasma p-Tau₂₁₇ in two diverse cohorts among whom 91% also underwent CSF analysis.

Objective

To determine the relationships between CSF and plasma phosphorylated tau (p-Tau) as biomarkers for Alzheimer's disease (AD), and identify factors influencing these relationships beyond renal dysfunction.

Design/Methods NHW (n=113), B/AA (n=66) and Chinese American (ChA, n=38) participants recruited from two universities were included in the study. We prospectively measured plasma and CSF p-Tau₂₁₇ levels using the updated Fujirebio Lumipulse assay, examined the correlation between CSF p-Tau₂₁₇ and CSF p-Tau₁₈₁ (same fluid, different epitope), how they correlated with plasma p-Tau₂₁₇ levels, and how these relationships are influenced by clinical, genetic (APOE genotype), demographic, neurodegenerative (neurofilament light chain), neuroinflammatory (sTREM2, sTNFR1, sTNFR2), and other CSF proteomic factors.

Results CSF p-Tau₁₈₁ strongly correlated with CSF p-Tau₂₁₇ (R²=0.912), and both CSF measures moderately correlated with plasma p-Tau₂₁₇ (R²=0.694). In a multi-variate model, plasma p-Tau₂₁₇ levels were independently associated with CSF p-Tau, cognitive impairment (higher with greater deficits), and racial background (lower in B/AA than NHW participants, but no difference between ChA and NHW participants). This resulted in greater positive predictive value for NHW than B/AA participants. Exploratory analysis showed this race-based difference could be mediated by differential involvement of complement or lysosomal pathways.

Conclusions Plasma p-Tau₂₁₇ levels are highly promising peripheral biomarkers during the initial screening for Alzheimer's disease, but should not be used without clinical assessment or consideration for other factors which influence its levels.

Authors/Disclosures
William T. Hu, MD, PhD, FAAN (Rutgers Biomedical and Health Sciences) PRESENTER	Dr. Hu has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Fujirebio. Dr. Hu has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Beckman Coulter. Dr. Hu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Apellis Pharmaceuticals. The institution of Dr. Hu has received research support from NIA. The institution of Dr. Hu has received research support from TMCity Foundation. The institution of Dr. Hu has received research support from Atlanta Family Foundation. The institution of Dr. Hu has received research support from Fujirebio Diagnostics.

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