Potential utility of plasma pTau217 for assessing amyloid and tau biomarker profiles

Abstract

Plasma phosphorylated tau 217 (pTau217) is a promising biomarker for Alzheimer’s disease, reflecting both amyloid β (Aβ) and tau positron emission tomography (PET) results. While its diagnostic role is actively being investigated, this study aims to expand its application to staging disease progression and predicting cognitive decline. A total of 2,919 participants, primarily diagnosed as Alzheimer’s clinical syndrome, were recruited. Plasma pTau217 was measured using the ALZpath assay, and its diagnostic accuracy for binary Aβ/tau (A/T) biomarker profiles and Aβ and tau PET staging was assessed using area under the curve (AUC). Longitudinal Mini-Mental State Examination (MMSE) changes according to plasma pTau217-based staging were analyzed. Plasma pTau217 accurately predicted binary Aβ (AUC 0.96) and tau (AUC 0.90) PET positivity. Both the Aβ-positive/tau-positive (A ptau +/T ptau +) and Aβ-positive/tau-negative (A ptau +/T ptau −) groups, defined using plasma pTau217 cutoffs, showed significantly worse MMSE trajectories compared to the Aβ-negative/tau-negative (A ptau −/T ptau −) group (for A ptau +/T ptau + vs. A ptau −/T ptau −, β = −1.061 ± 0.055; for A ptau +/T ptau − vs. A ptau −/T ptau −, β = −0.322 ± 0.070, all adjusted P < 0.001). However, its performance was less effective for Aβ and tau PET staging, particularly for medial temporal tau PET stage (AUC 0.71). Nevertheless, plasma pTau217-based staging distinguished longitudinal MMSE deterioration (all adjusted P < 0.001). Plasma pTau217 is effective for predicting A/T biomarker profile and cognitive decline, though further study is needed to better explain its association with Aβ and tau PET staging. Not applicable.