Pittsburgh plasma p-tau217: classification accuracies for autosomal dominant and sporadic Alzheimer's disease in the community.

INTRODUCTION: Most available p-tau217 immunoassays have similar performances. 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 employs an alternative antibody, and benchmarked the results against ALZpath-p-tau217. METHODS: Following 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 AUC=0.94, and Aβ-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 elevated in tau-PET-positive versus tau-PET-negative participants (P=0.06; AUC=0.71 for both). 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 AD, equivalent to the widely used ALZpath-p-tau217.