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.