Diagnostic and Prognostic Utility of Plasma p-tau217 for Alzheimer's Disease in Chinese Elderly: Insights From the SILCODE Study With a Derived Threshold

Abstract

Background: Plasma phosphorylated tau 217 (p-tau217) has emerged as a promising Alzheimer's disease (AD) biomarker, yet its longitudinal associations with neurodegeneration and cognitive decline remain inadequately characterized in Chinese populations, and ethnicity-specific diagnostic thresholds are lacking for optimal clinical application. Methods: A total of 541 participants (402 cognitively unimpaired [CU]; 139 cognitively impaired [CI]) from the Sino Longitudinal Study on Cognitive Decline (SILCODE) cohort were enrolled. Cross-sectional and longitudinal associations of plasma p-tau217 with amyloid-β (Aβ) pathology, neurodegeneration, and cognition were evaluated. Diagnostic thresholds were derived using receiver operating characteristic analysis, and Cox regression assessed prognostic value for clinical progression. Results: Cross-sectionally, baseline p-tau217 was associated with greater Aβ burden, neurodegeneration, and poorer cognition in the whole cohort and CI group; in the CU group, associations were confined to amyloid measures. Longitudinally, accelerated p-tau217 accumulation was associated with faster neurodegeneration and cognitive decline in the whole cohort, with stage-dependent patterns: nominal associations with neurodegenerative markers in CU and prominent cognitive associations in CI. Plasma p-tau217 demonstrated high diagnostic accuracy for amyloid positivity (AUC = 0.891; cutoff: 0.529 pg/mL). Threshold-based stratification effectively differentiated individuals by Aβ burden, neurodegeneration, and cognitive trajectories. Elevated baseline p-tau217 predicted higher progression risk (Whole cohort: HR = 2.66 [1.28–5.53], p = 0.009; CU: HR = 2.44 [1.07–5.59], p = 0.034). Conclusion: Plasma p-tau217 serves as a valuable diagnostic and prognostic biomarker for AD, even among CU individuals, and the ethnicity-specific threshold of 0.529 pg/mL enhances its clinical applicability for early detection and risk stratification in Chinese populations.