Blood phosphorylated tau for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis

Plasma phosphorylated tau (p-tau) biomarkers show promise to transform the clinical management of Alzheimer's disease by providing more accessible and cost-effective diagnostic tools. p-tau biomarkers have emerged as leading contenders for clinical implementation; however, there have been no comprehensive meta-analyses of their diagnostic performance. We aimed to evaluate the diagnostic performance of plasma p-tau biomarkers and individual p-tau assays to identify biologically defined Alzheimer's disease.

For this systematic review and meta-analysis, we searched Embase, MEDLINE, PubMed, Scopus, and Web of Science for articles published from July 1, 1984 up to Dec 9, 2024, that reported on the discriminative accuracy of plasma p-tau biomarkers for amyloid-PET, tau-PET, CSF, and neuropathological reference standards. We included cohort, case-control, cross-sectional, and randomised controlled studies that recruited adults from any setting. Articles were excluded if they did not contain data on a p-tau blood biomarker, did not contain an appropriate biological reference standard, did not report diagnostic accuracy data, included participants younger than 18 years, or reported duplicate or overlapping data from another publication. Summary data were independently extracted by eight authors. Risk of bias was assessed using QUADAS-2. The primary outcome was the diagnostic performance of plasma p-tau biomarkers for Alzheimer's disease. We used a bivariate random-effects meta-analysis to estimate pooled sensitivity, specificity, diagnostics odds ratio and area under the receiver operating characteristic curve. We assessed the certainty of evidence using GRADE. This study was done following PRISMA-DTA guidelines and is registered with PROSPERO as CRD42023422143.