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

Cerebrospinal fluid (CSF) biomarkers are used to identify or detect the condition of multiple neurodegenerative diseases, even psychiatric disorders. However, discordant results between observational studies 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, which contribute to the diagnosis of these diseases. Studies before September 2023 were searched based on databases. We included observational studies that compared the CSF levels of these biomarkers (Aβ 1-42 , tau, p-tau 181, and α-synuclein) between healthy controls, neurodegenerative diseases, and psychiatric disorders. We conducted traditional pairwise analysis and network meta-analysis to evaluate the evidence concerning these CSF biomarkers between these neurodegenerative diseases and psychiatric disorders. This network meta-analysis included 117 studies with 25210 patients to investigate the CSF biomarkers in multiple neurodegenerative diseases and psychiatric disorders (primarily depression, bipolar disorder, and schizophrenia). For CSF Aβ 1-42 levels, there were no statistically significant differences between these groups in network analysis. Regarding CSF t-tau and p-tau 181 levels, statistical significance was observed in comparing Alzheimer’s disease (AD) and other diseases, e.g., amyotrophic lateral sclerosis (ALS). Regarding CSF α-synuclein levels, statistical significance was observed in several comparisons, e.g., AD vs. ALS. Conclusively, we identified that CSF Aβ 1-42 , t-tau, and p-tau 181 might be promising markers distinguishing AD from other neurodegenerative diseases and cognitive impairment. It is conflicting that CSF α-synuclein acts as a marker for diagnosing neurodegenerative diseases and predicts the presence of psychiatric disorders.