Pittsburgh plasma p‐tau217: Classification accuracies for autosomal dominant and sporadic Alzheimer's disease in the community

INTRODUCTION

Most available phosphorylated tau (p‐tau)217 immunoassays have similar performance. It is unclear if this is due to the use of the same antibody (the “ALZpath antibody”). We established and evaluated a novel p‐tau217 assay that uses an alternative antibody and benchmarked the results against ALZpath‐p‐tau217.

METHODS

After development and analytical validation of the University of Pittsburgh (“Pitt‐p‐tau217”) method, clinical verification was performed in three independent cohorts ( n  = 363).

RESULTS

Pitt‐p‐tau217 demonstrated high between‐run stability, linearity, and specificity. Clinically, Pitt‐p‐tau217 differentiated neuropathologically confirmed PSEN1 mutation carriers from controls with area under the curve (AUC) = 0.94, and amyloid beta (Aβ) positron emission tomography (PET)–positive from Aβ PET–negative cognitively normal older adults with AUC up to 0.84, equivalent to ALZpath‐p‐tau217 results. Both Pitt‐p‐tau217 and ALZpath‐p‐tau217 were slightly elevated in tau PET–positive versus tau PET–negative participants. Between‐assay correlations were up to 0.93.

DISCUSSION

The new Pitt‐p‐tau217 assay exhibits high and reproducible classification accuracies for identifying individuals with biological evidence of Alzheimer's disease, equivalent to the widely used ALZpath‐p‐tau217.

Highlights

• We designed and developed an alternative assay to quantify plasma phosphorylated tau (p‐tau)217, aiming to enhance accuracy and enable early detection of Alzheimer's disease (AD).

• Comprehensive analytical and clinical validation demonstrated that the new p‐tau217 assay is a valuable and affordable resource for investigating AD pathophysiology.

• The new p‐tau217 assay showed similar performance to the established ALZpath assay in staging and monitoring early AD.