Diagnostic and analytical performance of plasma pTau181 and 217 in a clinical laboratory

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AbstractBackgroundBlood‐based biomarkers will be essential for providing clinicians an accessible and cost‐effective Alzheimer’s disease (AD) screening tool. Elevated levels of two phosphorylated tau biomarkers (pTau181 & pTau217) correlated with amyloid and tau‐PET consistent with AD diagnosis. We evaluated the analytical and clinical performance of each biomarkers using two different high‐sensitivity methodologies (CLEIA and Simoa®) in a single laboratory to compare the performance of pTau181 and 217 in a clinical (CLIA‐certified) laboratory.MethodPlasma pTau217 levels were measure using either the ALZpath pTau217 assay on the Quanterix HD‐X Simoa® platform or LUMIPULSE plasma pTau 217 on the Lumipulse G1200 platform. Plasma pTau181 levels were measured on the Simoa® platform using ADx Neurosciences antibodies.Analytical performance including sensitivity, linearity, precision, accuracy, cross‐reactivity, interference, and sample stability was determined at Neurocode’s CLIA laboratory using CLIA guidelines.Clinical testing was performed using a collection of amyloid PET confirmed samples (N = 260). And neuropathology confirmed samples collected from the University of British Columbia (UBC) at the time of initial diagnosis (N = 119).ResultpTau217 (AUC – 0.92 to 0.93) had enhanced clinical performance compared to pTau181 across platforms (AUC 0.81) and sample cohorts for diagnosing AD. pTau217 assays had a greater dynamic range (i.e. lower limit quantification) compared to pTau181, resulting in more substantial separation between lower‐limits and clinical decision points. pTau217 has a higher fold difference between PET positive and negative subjects regardless of methodology compared to pTau181. Sample stability was comparable across platforms and methodology. Between lot precision of pTau217 (≤ 13% CV) was improved compared to pTau181 (≤ 20% CV) on the Simoa platform.ConclusionIn conclusion, the superior clinical and analytical performance of pTau217 advocates for its use in clinical practice over pTau181. Plasma pTau217 is a robust screening tool that can be used by clinician for accurate and reliable Alzheimer's disease diagnosis.