The Alzheimer's Disease Diagnosis and Plasma Phospho‐Tau217 (ADAPT) study stage 1: Validating clinical cut‐points against CSF and amyloid PET

INTRODUCTION We validated plasma phosphorylated tau (p‐tau)217 cut‐points for Alzheimer's disease (AD) diagnosis using two commercial assays in two biomarker‐defined cohorts and examined influences of pre‐analytical factors and chronic kidney disease (CKD) on p‐tau217 concentrations. METHODS Lumipulse (Fujirebio) and ALZpath (Quanterix) assays quantified plasma p‐tau217 in symptomatic patients (AD status definition cerebrospinal fluid [CSF] n = 257; amyloid positron emission tomography [PET] n = 76). Receiver operating characteristic (ROC) analyses established ≥ 95% sensitivity/specificity cut‐points. In separate cohorts we evaluated the impact of pre‐analytical handling/transport variations ( n = 40/10) and cognitively normal (CN)‐CKD individuals ( n = 58). RESULTS Diagnostic accuracy was similar (area under the ROC Lumipulse 0.947; ALZpath 0.940). Lumipulse p‐tau217 achieved 95% sensitivity and 97% specificity using dual cut‐points (0.153/0.422 pg/mL), producing indeterminate results in 19.4% (CSF defined) and 34.2% (PET defined). P‐tau217 concentrations were stable across handling conditions and kit lots, and mostly in the low‐to‐intermediate range in CN‐CKD. DISCUSSION Lumipulse plasma p‐tau217, now available in our United Kingdom Accreditation Service–accredited clinical National Health Service laboratory, will be used in a randomized trial of p‐tau217 result disclosure in memory services.