Plasma p‐tau217 for Alzheimer's disease diagnosis: a memory clinic implementation approach

Abstract INTRODUCTION Plasma phosphorylated tau at threonine 217 (p‐tau217) has shown excellent diagnostic performance for Alzheimer's disease (AD), yet real‐world validation and implementation pathways remain limited. This study assessed its clinical applicability and proposed a practical workflow for memory clinics. METHODS Plasma p‐tau217, p‐tau181, and neurofilament light chain (NfL) were quantified in consecutive patients referred for cognitive assessment. Cerebrospinal fluid (CSF) amyloid beta (Aβ) 42/40 defined amyloid (A) status, and final etiological diagnoses were reached through multidisciplinary consensus integrating clinical, neuropsychological, and metabolic imaging data. RESULTS Among 163 patients (mean age 69.3 ± 7.4 years, 52% female), plasma p‐tau217 distinguished A+ from A− individuals (area under the curve [AUC] 0.90, 81% sensitivity, 91% specificity). AD patients showed the highest p‐tau217 levels, while non‐AD neurodegenerative disorders exhibited elevated NfL ( p < 0.001). A dual cut‐off strategy with 95% sensitivity and specificity could have avoided 65% of lumbar punctures. DISCUSSION Plasma p‐tau217 demonstrated robust clinical validity and supports structured integration into routine diagnostic pathways.