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.