P-tau231 as a Diagnostic Biomarker for Alzheimer's Disease and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis

OBJECTIVE: Some previous studies have shown that cerebrospinal fluid (CSF) levels of p-tau231 were significantly higher in patients with Alzheimer's disease (AD) compared to that in patients with mild cognitive impairment (MCI) and normal control (NC), whereas some other studies did not. Due to contradictory results, we aimed to conduct a systematic review and meta-analysis study on previous investigations to examine the potential role of CSF p-tau231 as a biomarker of AD and MCI. METHOD: PubMed, Scopus, and Web of Science were searched in March 2021 for studies on the CSF level of p-tau231 in AD, MCI, and NC. The statistical analysis was performed via standardized mean difference (SMD) methodology with a 95% confidence interval. RESULTS: A total of 10 studies including 1141 subjects were included. The present study showed that CSF level of p-tau231 was significantly higher in AD patients compared to that in MCI patients (SMD = 160.94 [11.11, 310.78], P = 0.04) and NC patients (SMD = 436.21 [164.88, 707.54], P < 0.00). Moreover, comparison of MCI and NC showed a significantly higher level of CSF p-tau231 in MCI compared to NC (SMD = 341.44 [59.73, 623.14], P = 0.02). CONCLUSION: P-tau231 showed to be a valuable biomarker of discrimination AD, MCI, and NC based on our findings. This meta-analysis showed that the CSF p-tau231 can reliably differentiate AD patients from MCI and NC patients. Furthermore, based on our findings the level of CSF p-tau231 was significantly higher in MCI compared to NC. Therefore, p-tau231 can be added to the list of potential biomarkers for the diagnosis of AD and MCI in further studies. However, further investigations are needed to confirm our findings.