ALZpath Dx: A novel accessible, validated, and scalable phosphorylated‐tau 217 (pTau217) assay in blood

Abstract

AbstractBackgroundBlood‐based biomarkers for phosphorylated tau demonstrate strong diagnostic accuracy and compare favorably with current corresponding CSF and neuroimaging biomarkers. Of the four major pTau assays in use (pTau181, pTau217, and pTau231, Nfl), pTau217 appears to be the most robust marker, consistently outperforming plasma pTau 181, neurofilament light, and imaging markers. pTau217 has been shown to correlate with post‐mortem AD pathology, with the ability to differentiate AD from other types of dementia and predict future progression from both normal cognition and mild cognitive impairment to AD.(1,2) Additionally, pTau217 can be used to monitor AD progression because longitudinal increases in pTau217 is indicative of worsening of brain atrophy and cognition in AD.(3) pTau217, therefore, represents a cost‐effective and accessible blood‐based biomarker for tau pathophysiology, that can transform the AD diagnostic field.MethodALZpath has developed reagents for pTau217 and establish a robust and scalable fit for purpose plasma‐based ultra‐sensitive assay utilizing a proprietary monoclonal pTau217 antibody.ResultThe ultra‐sensitive blood‐based ELISA assay, using a peptide calibrator, has been developed on the semi‐automated single‐molecule array Simoa® platform. The assay has been launched for clinical use as laboratory‐developed test (LDT). Evaluation in independent clinical cohorts with multiple co‐morbidities is currently being established to advance to an in‐vitro diagnostic (IVD).ConclusionThe ALZpath pTau217 Simoa® assay is now a fit for purpose validated assay now available for commercial use. Clinical use of this assay is described in Snyder et al. Gouda et al. and Ashton et al. AAIC 2023.