Evaluating plasma phosphorylated tau217 for clinical rule-out of cerebral amyloid pathology: Evidence from a memory clinic cohort

Background Plasma phosphorylated tau 217 (pTau217) is a promising biomarker for Alzheimer's disease amyloid-β (Aβ) pathology, but cut-offs require validation. Objective The aim was to evaluate the diagnostic performance of plasma phosphorylated tau 217 for identifying cerebral amyloid pathology to reduce the need for more invasive or resource-intensive confirmatory testing by identifying individuals with a low likelihood of amyloid pathology. Methods Elecsys ® pTau217 was evaluated in a memory clinic cohort using ROC analysis. Cut-offs were derived using sensitivity-weighted Euclidean distance and bootstrap resampling. Results pTau217 discriminated Aβ-positive from Aβ-negative individuals (AUC 0.854). The cut-off was 0.169 pg/mL (95% CI 0.140–0.200), with 87.7% sensitivity and 77.0% specificity. Age and sex adjustment did not improve performance. Conclusions The threshold was consistent with previously reported low cut-offs, supporting potential rule-out utility; however, its sensitivity precludes stand-alone exclusion of Aβ pathology in memory clinic populations.