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

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.

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.

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.

Plasma p-tau217 demonstrated robust clinical validity and supports structured integration into routine diagnostic pathways.