Cerebrospinal fluid biomarkers for the subtle differentiation of neurodegenerative diseases and psychiatric disorders: A systematic review with network meta-analysis

Abstract Background and purpose Cerebrospinal fluid (CSF) biomarkers are used to identify or detect the condition of multiple neurodegenerative diseases, even psychiatric disorders. However, discordant results between clinical trials failed to meet the expectations of identifying neurodegenerative diseases and psychiatric disorders. We conducted this systematic review and network meta-analyses to investigate the CSF biomarkers in neurodegenerative diseases and psychiatric disorders. Methods Studies before July 2021 were searched based on databases. We included clinical trials that compared the CSF levels of these biomarkers (Aβ1−42, tau, p-tau181, and α-synuclein) between the healthy controls, neurodegenerative diseases, and psychiatric disorders. We conducted traditional pair-wise analysis and network meta-analysis to evaluate the evidence concerning these CSF biomarkers between these neurodegenerative diseases and psychiatric disorders. Results This network meta-analysis included 117 studies with 25210 patients to investigate the CSF biomarkers in multiple neurodegenerative diseases and psychiatric disorders. For CSF Aβ1−42 levels, there were no statistically significant differences between these groups in network analysis. Regarding CSF t-tau and p-tau181 levels, statistical significance was observed in the comparisons between AD and other diseases, e.g., ALS. Regarding CSF α-synuclein levels, statistical significance was observed in several comparisons, e.g., AD vs. ALS. Conclusions We identified that CSF Aβ1−42, t-tau, and p-tau181 might be promising markers distinguishing AD from other neurodegenerative diseases and cognitive impairment. It is conflicted that CSF α-synuclein acts as the marker for diagnosing neurodegenerative diseases and predicts the presence of psychiatric disorders.