Plasma p-tau217 predicts PET-based pathological staging for precision Alzheimer disease assessment.

INTRODUCTION: While positron emission tomography (PET) is the standard for pathological staging, its limited availability necessitates accessible alternatives. We evaluated plasma biomarkers for detecting PET-based stages using single-axis (Thal/Braak) and integrated A/T composite models. METHODS: We enrolled 237 AD spectrum participants undergoing multimodal assessments including amyloid/tau PET and plasma biomarker analysis (phosphorylated tau [p-tau] 217, %p-tau217, and amyloid beta [Aβ] 42/40 ratio). Detecting and discriminative performance was assessed using receiver operating characteristics (ROC) analysis and probability-based stage prediction. RESULTS: Plasma p-tau217-based biomarkers showed excellent detecting performance for early amyloid (Thal I-II; area under the curve values > 0.96) and intermediate tau (Braak III-IV; area under the curve values > 0.92). Probability-based prediction identified therapeutic window thresholds of 1.895-5.077 pg/mL. Notably, integrated A/T composite staging yielded highly consistent thresholds (< 3% variance). DISCUSSION: Plasma p-tau217-based biomarkers accurately reflect PET-based staging across frameworks. The convergent therapeutic window thresholds demonstrate robust biological transitions, enabling accessible identification of optimal candidates for disease-modifying therapies.