Diagnostic and prognostic performance to detect Alzheimer’s disease and clinical progression of a novel assay for plasma p-tau217

Background: Recent advances in disease-modifying treatments highlight the need for accurately identifying individuals in early Alzheimer’s disease (AD) stages and for monitoring of treatment effects. Plasma measurements of phosphorylated tau (p-tau) are a promising biomarker for AD, but different assays show varying diagnostic and prognostic accuracies. The objective of this study was to determine the clinical performance of a novel plasma p-tau217 (p-tau217) assay, p-tau217+ _Janssen, and perform a head-to-head comparison to an established assay, plasma p-tau217 _Lilly, within two independent cohorts _. Methods: The study consisted of two cohorts, cohort 1 (27 controls and 25 individuals with mild-cognitive impairment [MCI]) and cohort 2 including 147 individuals with MCI at baseline who were followed for an average of 4.92 (SD 2.09) years. Receiver operating characteristic analyses were used to assess the performance of both assays to detect amyloid-β status (+/−) in CSF, distinguish MCI from controls, and identify subjects who will convert from MCI to AD dementia. General linear and linear mixed-effects analyses were used to assess the associations between p-tau and baseline, and annual change in Mini-Mental State Examination (MMSE) scores. Spearman correlations were used to assess the associations between the two plasma measures, and Bland-Altmann plots were examined to assess the agreement between the assays. Results: Both assays showed similar performance in detecting amyloid-β status in CSF (plasma p-tau217+ _Janssen AUC = 0.91 vs plasma p-tau217 _Lilly AUC = 0.89), distinguishing MCI from controls (plasma p-tau217+ _Janssen AUC = 0.91 vs plasma p-tau217 _Lilly AUC = 0.91), and predicting future conversion from MCI to AD dementia (plasma p-tau217+ _Janssen AUC = 0.88 vs p-tau217 _Lilly AUC = 0.89). Both assays were similarly related to baseline (plasma p-tau217+ _Janssen rho = −0.39 vs p-tau217 _Lilly rho = −0.35), and annual change in MMSE scores (plasma p-tau217+ _Janssenr = −0.45 vs p-tau217 _Lillyr = −0.41). Correlations between the two plasma measures were rho = 0.69, p < 0.001 in cohort 1 and rho = 0.70, p < 0.001 in cohort 2. Bland-Altmann plots revealed good agreement between plasma p-tau217+ _Janssen and plasma p-tau217 _Lilly in both cohorts (cohort 1, 51/52 [98%] within 95%CI; cohort 2, 139/147 [95%] within 95%CI). Conclusions: Taken together, our results indicate good diagnostic and prognostic performance of the plasma p-tau217+ _Janssen assay, similar to the p-tau217 _Lilly assay.