Diagnostic utility of cerebrospinal fluid α-synuclein in Parkinson's disease: A systematic review and meta-analysis

Background: The accumulation of misfolded α-synuclein aggregates is associated with PD. However, the diagnostic value of the α-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 α-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 I2. 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 α-synuclein species in PD did not show significant differences with respect to the levels found in other parkinsonisms. Total α-synuclein was significantly reduced in PD when compared with controls (standardized mean differences −0.48; P <.001, I2 = 60%). Oligomeric (standardized mean differences 0.57; P <.001, I2 = 44%) and phosphorylated α-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 α-synuclein, and 0.71 and 0.64, respectively, for oligomeric α-syn. Conclusion: Most of the studies were at high risk of bias and have concerns regarding applicability. Diagnostic performance of CSF α-synuclein species is still below what would be considered acceptable for their introduction in clinical practice. Future research should focus on combining α-synuclein species with other biochemical markers as well on improving the standardization of current assays. © 2017 International Parkinson and Movement Disorder Society.