Clinical decision points for two plasma p-tau217 laboratory developed tests in neuropathology confirmed samples.

Introduction: We evaluated the diagnostic performance of two commercial plasma p-tau217 immunoassays compared to cerebrospinal fluid (CSF) testing and neuropathology.

Methods: One hundred and seventy plasma samples from the University of British Columbia Hospital Clinic for Alzheimer's (AD) and Related Disorders were analyzed for p-tau217 using Fujirebio and ALZpath assays. Decision points were determined using CSF testing and autopsy findings as the standard.

Results: Fujirebio and ALZpath p-tau217 had similar overall analytical and clinical performance, with distinct decision points for each assay. Based on autopsy findings, both p-tau217 assays identified individuals with AD from other neurodegenerative diseases (ALZpath area under the curve [AUC] = 0.94, Fujirebio AUC = 0.90). The ALZpath assay detected AD pathology at milder disease stages compared to the Fujirebio assay.

Discussion: Our study reinforces the clinical utility of plasma p-tau217 as an AD biomarker. Differences in test performance and clinical decision points suggest an assay-specific diagnostic approach is required for plasma p-tau217 in clinical practice.

Highlights: Two commercially available p-tau217 immunoassays (ALZpath and Fujirebio) showed equal performance based on CSF testing.ALZpath p-tau217 showed higher performance compared to Fujirebio p-tau217 based on AD diagnosis by neuropathology confirmation.Specific plasma p-tau217 assays may require distinct decision points for AD screening, diagnosis, and disease progression monitoring.