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