Little Evidence Supports CSF α-Synuclein as a Diagnostic Tool for Parkinson Disease

cerebrospinal fluid csf
cerebrospinal fluid csf
The diagnosis of Parkinson disease is made mostly through a clinical assessment of motor signs and symptoms, which appear when approximately 70% of nigral neurons are lost.

Low levels of cerebrospinal fluid (CSF) α-synuclein (α-syn) are common in patients with Parkinson disease (PD), yet using the levels of α-syn as a diagnostic tool in clinical practice is not supported by current large-scale evidence, according to a systematic review and meta-analysis published in Movement Disorders.

According to the findings, which examined 34 studies on CSF total oligomeric and phosphorylated α-syn levels in patients with PD, investigators discovered that total α-syn levels are significantly reduced in patients with PD vs healthy controls (standardized mean differences [SMD] -0.48; P <.001, I2 = 60%).

In addition, oligomeric (SMD 0.57; P <.001, I2 = 44%) and phosphorylated α-syn (SMD 0.86; P <.001) were also higher in those with PD. 

Among 7 studies that were at a risk for bias, oligomeric α-syn concentrations were increased in patients with PD (SMD 0.57; 95% CI, 0.34-0.79; P <.001), confirmed by comparisons between healthy controls and patients with PD (SMD 0.65; 95% CI, -0.33 to 0.98; P <.001) and other neurologic conditions (SMD 0.54; 95% CI, 0.23-0.84; P <.01).

Despite these findings, investigators explained that current research does not support the use of CSF α-syn species as a diagnostic tool in clinical practice. Many of the studies assessing CSF α-syn levels in PD are at high risk for bias and present issues regarding applicability to real-world patients.

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The investigators of this study suggest that future research may need to “focus on combining CSF α-syn species with other biochemical markers” to improve diagnostic assessments for patients at risk for PD.


Eusebi P, Giannandrea D, Biscetti L, et al. Diagnostic utility of cerebrospinal fluid α-synuclein in Parkinson’s disease: a systematic review and meta-analysis [published online September 7, 2017]. Mov Disord. doi:10.1002/mds.27110