Clinical Utility of Plasma P-tau217 in Identifying Abnormal Brain Amyloid Burden in an Asian Cohort with High Prevalence of Concomitant Cerebrovascular Disease

Introduction: Using an Asian cohort with high prevalence of concomitant cerebrovascular disease (CeVD), we evaluated the performance of a plasma immunoassay for tau phosphorylated at threonine 217 (p-tau217) in detecting amyloid beta positivity (Aβ+) on positron emission tomography and cognitive decline, based on a three-range reference, which stratified patients into low-, intermediate-, and high-risk groups for Aβ+.

Methods: Brain amyloid status (Aβ- [n = 142] vs Aβ+ [n = 73]) on amyloid PET scans was assessed along with the plasma ALZpath p-tau217 assay to derive three-range reference points for PET Aβ+ based on 90% sensitivity (lower threshold) and 90% specificity (upper threshold).

Results: Plasma p-tau217 (area under the curve [AUC] = 0.923) outperformed routine clinical assessments (AUC = 0.760-0.819; p ≤ 0.003) and other plasma biomarkers (AUC = 0.817-0.834; p < 0.001). The high-risk group showed significantly higher rates of cognitive decline than the low-risk group.

Discussion: Risk stratification for PET Aβ+ based on a plasma p-tau217 assay demonstrated potential diagnostic and prognostic utility in an Asian cohort with concomitant CeVD.

Highlights: The utility of plasma p-tau217 to detect brain amyloid beta pathology (Aβ+) was studied in an Asian cohort with concomitant cerebrovascular disease Plasma tau phosphorylated at threonine 217 (p-tau217) showed superior utility in detecting Aβ+ compared to neuroimaging measures, clinical workup, or other blood biomarkers including p-tau181, glial fibrillary protein (GFAP), and Aβ Higher plasma p-tau217 correlated with faster cognitive decline Plasma p-tau217 shows promise as an Alzheimer's disease (AD) diagnostic and prognostic biomarker in diverse populations.