The Associations of Phosphorylated Tau 181 and Tau 231 Levels in Plasma and Cerebrospinal Fluid with Cognitive Function in Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Abstract

Background: Cerebrospinal fluid (CSF) or blood biomarkers like phosphorylated tau proteins (p-tau) are used to detect Alzheimer’s disease (AD) early. Increasing studies on cognitive function and blood or CSF p-tau levels are controversial. Objective: Our study examined the potential of p-tau as a biomarker of cognitive status in normal control (NC), mild cognitive impairment (MCI), and AD patients. Methods: We searched PubMed, Cochrane, Embase, and Web of Science for relevant material through 12 January 2023. 5,017 participants from 20 studies—1,033 AD, 2,077 MCI, and 1,907 NC—were evaluated. Quantitative analysis provided continuous outcomes as SMDs with 95% CIs. Begg tested publication bias. Results: MCI patients had lower CSF p-tau181 levels than AD patients (SMD =−0.60, 95% CI (−0.85, −0.36)) but higher than healthy controls (SMD = 0.67). AD/MCI patients had greater plasma p-tau181 levels than healthy people (SMD =−0.73, 95% CI (−1.04, −0.43)). MCI patients had significantly lower p-tau231 levels than AD patients in plasma and CSF (SMD =−0.90, 95% CI (−0.82, −0.45)). MCI patients showed greater CSF and plasma p-tau231 than healthy controls (SMD = 1.34, 95% CI (0.89, 1.79) and 0.43, (0.23, 0.64)). Plasma p-tau181/231 levels also distinguished the three categories. MCI patients had higher levels than healthy people, while AD patients had higher levels than MCI patients. Conclusions: CSF p-tau181 and p-tau231 biomarkers distinguished AD, MCI, and healthy populations. Plasma-based p-tau181 and p-tau231 biomarkers for AD and MCI need further study.