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ABSTRACT 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 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 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, I 2 = 60%). Oligomeric (standardized mean differences 0.57; P < .001, I 2 = 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
Eusebi et al. (Thu,) studied this question.