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

Abstract

Abstract 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.

Keywords

• Alzheimer's disease
• CSF Aβ 42 to 40 ratio
• CSF p‐tau181
• immunoassays
• neuropathology diagnosis
• plasma p‐tau217