Predictive Ability of Plasma p-tau217 for β-Amyloid Status: A Prospective Multicenter Study

Plasma tau phosphorylated at threonine 217 (p-tau217) measured with fully automated platforms has shown high accuracy for Alzheimer's disease (AD) diagnosis, but real-world multicenter data remain limited. We aimed to validate the diagnostic performance of p-tau217 for identifying AD pathology in a real-world multicenter cohort across seven memory clinics in Catalonia (Spain), with only one tertiary hospital with prior experience in AD blood-based biomarkers.

In this prospective multicenter study, consecutive patients with cognitive impairment undergoing routine cerebrospinal fluid (CSF) biomarker testing were included. Plasma samples were collected following a standardized pre-analytical protocol and analyzed centrally using the Lumipulse G p-tau217 assay (Fujirebio). Diagnostic accuracy for Aβ status was assessed overall and across sites.

A total of 185 participants were included. Plasma p-tau217 showed excellent accuracy for CSF-defined Aβ status (AUC 0.916) with consistent performance across centers. Using a single cut-off, diagnostic accuracy reached 84.9%, which prompted the use of a dual-threshold strategy to improve overall performance and to classify p-tau217 values into low, intermediate, and high probability categories of Aβ positivity. When applying a strict model with 97.5% sensitivity and specificity (cut-offs 0.146/0.486 pg/mL), 42.7% of participants fell within the intermediate zone, whereas the remaining 57.3% were confidently classified with 95.3% accuracy.

In a real-world multicenter memory-clinic cohort, plasma p-tau217 measured on a fully automated platform accurately discriminated CSF Aβ status and enabled reliable rule-in/rule-out classification in over half of patients. These findings support its broader clinical use as an initial diagnostic tool for AD.