Clinical and analytical comparison of three assays for plasma p‐tau isoforms on an ultrasensitive platform

Background Plasma phosphorylated Tau (P‐tau) protein is a promising biomarker for early detection of Alzheimer’s Disease (AD), reflecting abnormal tau metabolism in CSF and brain. Different Tau isoforms have been shown as specific biomarkers to detect AD including plasma tau phosphorylated at threonine 181 (P‐tau181) and at threonine 217 (P‐tau217). Novel plasma tests have been developed on various platforms for different isoforms and using various reagents, but these have not been compared directly for their analytical and clinical performance. In this study, we directly compared three novel P‐tau blood assays to investigate the clinical and technical differences between each assay. Method We included the following assays: plasma P‐tau181 from Quanterix, P‐tau181 Lilly and P‐tau217 Lilly assays, all run on the Simoa HD‐X (Quanterix). We analytically compared the novel assays for the parameters: precision, linearity, parallelism, limit of detection, recovery and sensitivity. The clinical performance of each assay was evaluated using plasma samples from 40 non‐demented healthy individuals of www.hersenonderzoek.nl (median age 66 years, 68 % females) and 40 AD‐dementia cases of the Amsterdam dementia cohort (median age 66, 60 % females). Using a receiver operating characteristics (ROC) curve analysis , we compared the discriminatory ability of each assay. Here, we present the clinical performance results. Result Plasma P‐tau217 and both plasma P‐tau181 assays were highly correlated, with correlation coefficients over 0.82 (all p< 0.001). Patients with AD‐dementia showed elevated levels of P‐tau181 and P‐tau217 in comparison to healthy controls (P‐tau 217 AUC = 0.995 (0.986‐1.00), P‐tau181 Quanterix AUC=0.936 (0.885‐987), P‐tau 181 Lilly AUC= 0.938 (0.87‐1.00)). The P‐tau217 Lilly assay numerically outperformed both the P‐tau 181 assays in discriminating between AD‐dementia and control cases with a sensitivity of 97.5% at a specificity of 95%. The P‐tau181 Quanterix and Lilly showed a sensitivity of 100% at 89.5%, 79% specificity, respectively. Conclusion Our findings suggest that the novel plasma P‐tau isoform tests are useful for the diagnostic work up of AD‐dementia.