The performance of plasma phosphorylated tau231 in detecting Alzheimer's disease: A systematic review with meta‐analysis

Abstract Cerebrospinal fluid (CSF) phosphorylated tau231 (P‐tau231) is associated with neuropathological outcomes of Alzheimer's disease (AD). The invasive access of cerebrospinal fluid has greatly stimulated interest in the identification of blood‐based P‐tau231, and the recent advent of single‐molecule array assay for the quantification of plasma P‐tau231 may provide a turning point to evaluate the usefulness of P‐tau231 as an AD‐related biomarker. Yet, in the plasma P‐tau231 literature, findings with regard to its diagnostic utility have been inconsistent, and thus, we aimed to statistically investigate the potential of plasma P‐tau231 in the context of AD via meta‐analysis. Publications on plasma P‐tau231 were systematically retrieved from PubMed, EMBASE, the Cochrane library and Web of Science databases. A total of 10 studies covering 2007 participants were included, and we conducted random‐effect or fixed‐effect meta‐analysis, sensitivity analysis and publication bias analysis using the STATA SE 14.0 software. According to our quantitative integration, plasma P‐tau231 increased from cognitively unimpaired (CU) populations to mild cognitive impairment to AD and showed significant changes in pairwise comparisons of AD, mild cognitive impairment and CU. Plasma P‐tau231 level was significantly higher in CU controls with positive amyloid‐β (Aβ) status compared with Aβ‐negative CU group. Additionally, the excellent diagnostic accuracy of plasma P‐tau231 for asymptomatic Aβ pathology was verified by the pooled value of area under the receiver operating characteristic curves (standard mean difference [95% confidence interval]: .75 [.69, .81], P < 0.00001). Overall, the increased plasma P‐tau231 concentrations were found in relation to the early development and progression of AD.