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

Eur J Neurosci. 2023 Aug;58(4):3132-3149. doi: 10.1111/ejn.16085. Epub 2023 Jul 27.

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.

Keywords: Alzheimer's disease; biomarker; dementia; meta-analysis; mild cognitive impairment; tau phosphorylation.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Alzheimer Disease* / cerebrospinal fluid
  • Alzheimer Disease* / diagnosis
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers
  • Cognitive Dysfunction* / diagnosis
  • Humans
  • tau Proteins / cerebrospinal fluid

Substances

  • tau Proteins
  • Amyloid beta-Peptides
  • Biomarkers