title: Cerebrospinal fluid alpha-synuclein as a biomarker for Parkinson's disease diagnosis: a systematic review and meta-analysis.
abstract: To date, there are no definitive biomarkers for Parkinson's disease (PD) diagnosis. The detection of cerebrospinal fluid (CSF) alpha (α)-synuclein in PD patients has yielded promising but inconclusive results. To determine the performance of CSF α-synuclein as a diagnostic biomarker of PD and whether CSF α-synuclein can discriminate PD from other neurodegenerative diseases, a systematic search of all relevant studies investigating reproducible CSF α-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 α-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 α-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 α-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 α-synuclein may be a biomarker for the diagnosis of PD. The use of α-synuclein alone however is not sufficient as a single biomarker and it must therefore be used in conjunction with other documented and reliable biomarkers.
authors.affiliation: Department of Neurology, Guangdong Neuroscience Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Gao
authors.forename: Hongmei
authors.initials: H
authors.lastname: Tang
authors.forename: Kun
authors.initials: K
authors.lastname: Nie
authors.forename: Limin
authors.initials: L
authors.lastname: Wang
authors.forename: Jiehao
authors.initials: J
authors.lastname: Zhao
authors.forename: Rong
authors.initials: R
authors.lastname: Gan
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Ruiming
authors.initials: R
authors.lastname: Zhu
authors.forename: Shujun
authors.initials: S
authors.lastname: Feng
authors.forename: Zhenpeng
authors.initials: Z
authors.lastname: Duan
authors.forename: Yuhu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
mesh_terms: D015415:Biomarkers / Q000134:cerebrospinal fluid*; D006801:Humans; D010300:Parkinson Disease / Q000134:cerebrospinal fluid*; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; D051844:alpha-Synuclein
keywords: Parkinson's disease; biomarker; cerebrospinal fluid; meta-analysis; α-synuclein