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

초록

Background and aims: Plasma phosphorylated tau (pTau) 217 is a promising biomarker for Alzheimer's disease, reflecting both amyloid β (Aβ) and tau PET results. While its diagnostic role is actively being investigated, this study aims to expand its application to staging disease progression and predicting cognitive outcomes. Methods: A total of 2919 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 (AT) biomarker profiles and topographic PET stages was assessed using area under the curve (AUC). Longitudinal Mini-Mental State Examination (MMSE) changes according to plasma pTau217-based staging were analyzed. Results: Plasma pTau217 accurately predicted binary Aβ (AUC 0.95) and tau (AUC 0.88) PET positivity, and both Aptau+/Tptau + (β = −1.061 ± 0.055, adjusted P < 0.001) and Aptau+/Tptau- (β = −0.322 ± 0.070, adjusted P < 0.001) groups showed significantly worse MMSE trajectories compared to the Aptau−/Tptau- group. However, its performance was less effective for Aβ and tau PET topographic staging, particularly for medial-temporal tau PET stage (AUC 0.62). Nevertheless, plasma pTau217-based staging distinguished longitudinal MMSE deterioration (all adjusted P < 0.001). Conclusions: Plasma pTau217 is effective for predicting AT profile and cognitive decline, though further study is needed to better explain its association with topographic PET staging.