Diagnostic Utility of Cerebrospinal Fluid α-Synuclein in Parkinson's Disease: A Systematic Review and Meta-Analysis

Background: The accumulation of misfolded alpha-synuclein aggregates is associated with PD. However, the diagnostic value of the alpha-synuclein levels in CSF is still under investigation. Methods: A comprehensive search of the literature was performed, yielding 34 studies eligible for meta-analysis. We included studies that reported data on CSF total, oligomeric and phosphorylated alpha-synuclein in patients with PD and healthy participants, neurological controls, or other parkinsonisms. Standardized mean differences were pooled using random-effects models, and heterogeneity was reported as I-2. Bivariate random effects meta-analysis was also performed on diagnostic data. Methodological quality of the selected studies was assessed using the QUADAS-2 tool. Results: Concentrations of alpha-synuclein species in PD did not show significant differences with respect to the levels found in other parkinsonisms. Total alpha-synuclein was significantly reduced in PD when compared with controls (standardized mean differences -0.48; P < .001, I-2 = 60%). Oligomeric (standardized mean differences 0.57; P < .001, I-2 = 44%) and phosphorylated alpha-synuclein (standardized mean differences 0.86; P < .001) were significantly increased in PD when compared with controls. Sensitivity and specificity for distinguishing PD and controls were 0.72 and 0.65, respectively, for total alpha-synuclein, and 0.71 and 0.64, respectively, for oligomeric alpha-syn. Conclusion: Most of the studies were at high risk of bias and have concerns regarding applicability. Diagnostic performance of CSF alpha-synuclein species is still below what would be considered acceptable for their introduction in clinical practice. Future research should focus on combining alpha-synuclein species with other biochemical markers as well on improving the standardization of current assays. (c) 2017 International Parkinson and Movement Disorder Society