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.

Activation of tyrosine kinase c-Abl contributes to α-synuclein–induced neurodegeneration

“…Phosphoserine 129 α-synuclein has been investigated as a potential biomarker in PD, and its concentrations correlated weakly with PD severity (44). In addition, α-synuclein levels alone are not sufficient as a PD biomarker (45). Combined total α-synuclein and phosphoserine 129 α-synuclein levels might distinguish different parkinsonian disorders (44).…”

“…Combined total α-synuclein and phosphoserine 129 α-synuclein levels might distinguish different parkinsonian disorders (44). Thus, the utility of total α-synuclein and serine 129 phosphorylation of α-synuclein does not seem to be overly promising (44,45). In particular, phosphoserine 129 α-synuclein does seem to be a suitable progression marker in human PD; whether it will be suitable as a diagnostic marker requires further study (44).…”

The role of autophagy in neurotoxicity caused by extracellular ASYN

“…Najnovija istraživanja pokazuju da ASYN nije isključivo unutarćelijski protein, kao što se ranije smatralo, već da promene u koncentraciji ovog proteina mogu da se otkriju i u cerebrospinalnoj tečnosti obolelih od PB (3). Pokazano je i da se ASYN može preneti sa neurona na neuron (4), što ukazuje na to da je mogući mehanizam širenja PB sličan patogenetskom mehanizmu širenja prionskih proteina (5,6).…”

Recent advances in biomarkers for Parkinson’s disease focusing on biochemicals, omics and neuroimaging

“…However, neither plasma nor CSF α-synuclein is presently a reliable marker of PD, as abnormal α-synuclein accumulation is commonly used as a marker of a group of diseases called synucleinopathies [43,44]. It should more readily distinguish PD from tauopathies, such as PSP or AD, but would not distinguish PD so easily from DLB or MSA.…”

“…It should more readily distinguish PD from tauopathies, such as PSP or AD, but would not distinguish PD so easily from DLB or MSA. In order to develop a diagnostic test or a biomarker for PD, more detailed studies are needed on different modified forms of α-synuclein from different peripheral tissues for their potential as a surrogate marker of CSF or plasma α-synuclein [43,44].…”