Plasma tau proteins for the diagnosis of mild cognitive impairment and Alzheimer's disease: A systematic review and meta-analysis

Objective: Detecting plasma tau biomarkers used to be impossible due to their low concentrations in blood samples. Currently, new high-sensitivity assays made it a reality. We performed a systematic review andmeta-analysis in order to test the accuracy of plasma tau protein in diagnosing Alzheimer's disease (AD) or mild cognitive impairment (MCI). Methods: We searched PubMed, Cochrane, Embase and Web of Science databases, and conducted correlation subgroup analysis, sensitivity analysis and publication bias analysis using R Programming Language. Results: A total of 56 studies were included. Blood t-tau and p-tau levels increased fromcontrols toMCI to AD patients, and showed significant changes in pairwise comparisons of AD, MCI and normal cognition. P-tau217 was more sensitive than p-tau181 and p-tau231 in di erent cognition periods. In addition, ultrasensitive analytical platforms, immunomagnetic reduction (IMR), increased the diagnostic value of tau proteins, especially the diagnostic value of t-tau. Conclusion: Both t-tau and p-tau are suitable AD blood biomarkers, and p-tau217 is more sensitive than other tau biomarkers to di erentiate MCI and AD. Detection techniques also have an impact on biomarkers' results. New ultrasensitive analytical platforms of IMR increase the diagnostic value of both t-tau and p-tau biomarkers. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, registration number: CRD42021264701