Diagnostic accuracy of plasma p‐tau217/Aβ42 for Alzheimer's disease in clinical and community cohorts

Abstract INTRODUCTION This study was undertaken to evaluate the diagnostic performance of a novel plasma phosphorylated tau (p‐tau) 217/amyloid beta (Aβ) 42 ratio test for Alzheimer's disease (AD). METHODS The diagnostic performance of the Lumipulse G plasma p‐tau217/Aβ42 ratio was evaluated using Aβ and tau positron emission tomography (PET) as reference standards in a clinic cohort ( n = 391) and a community cohort ( n = 121). RESULTS Plasma p‐tau217/Aβ42 exhibited high performance for abnormal statuses of Aβ PET (area under the curve [AUC]: 0.963 to 0.966) and tau PET (AUC: 0.947 to 0.974), which were clinically equivalent to those of cerebrospinal fluid (CSF) p‐tau181/Aβ42 and Aβ42/Aβ40 and higher than those of blood p‐tau217, Aβ42/Aβ40, p‐tau181, and p‐tau181/Aβ42 in both clinic and community cohorts. Applying a two‐cutoff approach improved the specificity without reducing sensitivity. The p‐tau217/Aβ42 ratio had a lower intermediate percentage than p‐tau217 alone in both clinic (10.6% vs 13.0%) and community (16.5% vs 31.4%) cohorts. DISCUSSION Plasma p‐tau217/Aβ42 has high performance in detecting cerebral AD pathologies, thus offering a promising tool for clinical diagnosis and community screening of AD. Highlights Lumipulse G plasma p‐tau217 and the p‐tau217/Aβ42 ratio accurately identified abnormal Aβ and tau PET statuses in both clinical and community cohorts. The performance of plasma p‐tau217 and p‐tau217/Aβ42 ratio were equivalent to CSF tests. Plasma p‐tau217/Aβ42 ratio outperformed p‐tau217 alone in identifying Aβ PET positivity, and this superiority is more obvious in the community cohort, suggesting an advantage in the early diagnosis of AD. Two cut points of p‐tau217/Aβ42 were established in the Chinese population for clinical laboratory and community screening uses.