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

Area of Science:

• Neurodegenerative disease research
• Biomarker discovery
• Alzheimer's disease diagnostics

Background:

• Positron emission tomography (PET) is the gold standard for Alzheimer's disease (AD) pathological staging.
• Limited PET availability necessitates accessible diagnostic alternatives.
• Plasma biomarkers are emerging as promising tools for AD staging.

Purpose of the Study:

• To evaluate plasma biomarkers for detecting PET-based pathological stages in AD.
• To assess performance using single-axis (Thal/Braak) and integrated A/T composite models.
• To identify accessible alternatives to PET for AD staging.

Main Methods:

• 237 participants with AD spectrum pathology were enrolled.
• Multimodal assessments included amyloid/tau PET and plasma biomarker analysis (p-tau217, %p-tau217, Aβ42/40 ratio).
• Receiver operating characteristics (ROC) analysis and probability-based stage prediction were used.

Main Results:

• Plasma p-tau217 demonstrated excellent detection for early amyloid (Thal I-II) and intermediate tau (Braak III-IV) pathology.
• Probability-based prediction identified therapeutic window thresholds (1.895-5.077 pg/mL).
• Integrated A/T composite staging showed highly consistent thresholds with <3% variance.

Conclusions:

• Plasma p-tau217 biomarkers accurately mirror PET-based staging across different models.
• Convergent therapeutic window thresholds indicate robust biological transitions.
• Plasma biomarkers enable accessible identification of optimal candidates for disease-modifying therapies.