Cerebrospinal fluid alpha-synuclein as a biomarker for Parkinson's disease diagnosis: a systematic review and meta-analysis

To date, there are no definitive biomarkers for Parkinson's disease (PD) diagnosis. The detection of cerebrospinal fluid (CSF) alpha (alpha)-synuclein in PD patients has yielded promising but inconclusive results. To determine the performance of CSF alpha-synuclein as a diagnostic biomarker of PD and whether CSF alpha-synuclein can discriminate PD from other neurodegenerative diseases, a systematic search of all relevant studies investigating reproducible CSF alpha-synuclein quantification methods was conducted in electronic databases. A total of 17 studies that included 3311 patients were included in this systemic review and meta-analysis. The mean CSF alpha-synuclein concentration was significantly lower in PD patients compared to normal/neurological controls [weighted mean difference (WMD) -0.31; 95% CI, -0.45, -0.16; p < 0.0001] and patients with Alzheimer's disease (AD) [WMD -0.15; 95% CI, -0.26, -0.04; p < 0.0001]. There was no significant difference between PD patients and dementia with Lewy bodies (DLB) patients [WMD -0.03; 95% CI, -0.16, 0.09; p = 0.58] or patients with multiple system atrophy (MSA) [WMD 0.05; 95% CI, -0.04, 0.13; p = 0.25]. Sensitivity and specificity of CSF alpha-synuclein in the diagnosis of PD was 0.88 (95% CI, 0.84-0.91) and 0.40 (95% CI, 0.35-0.45), respectively. The positive and negative likelihood ratios of CSF alpha-synuclein in the diagnosis of PD were 1.41 (95% CI, 1.24-1.60), and 0.29 (95% CI, 0.15-0.56), respectively. The corresponding summary receiver operating characteristic (SROC) curve showed an area under the curve (AUC) of 0.73. The concentration of CSF alpha-synuclein may be a biomarker for the diagnosis of PD. The use of alpha-synuclein alone however is not sufficient as a single biomarker and it must therefore be used in conjunction with other documented and reliable biomarkers.