Plasma alpha-synuclein levels in patients with Parkinson’s disease: a systematic review and meta-analysis

  • Anastasia BougeaEmail author
  • Leonidas Stefanis
  • George P Paraskevas
  • Evangelia Emmanouilidou
  • Kostas Vekrelis
  • Elisabeth Kapaki
Review Article



To date, there are no definitive biomarkers for diagnose Parkinson’s disease (PD). The detection of α-synuclein (α-Syn) in plasma of PD patients has yielded promising but inconclusive results. To determine the performance of α-Syn as a diagnostic biomarker of PD, we used a meta-analysis.


We identified 173 studies through a systematic literature review. From those, only studies reporting data on total α-Syn levels were included in the meta-analysis (10 publications, 1302 participants). Quality of studies was assessed by Newcastle-Ottawa scale.


The α-Syn levels were significantly higher in PD patients than healthy controls (standardized mean difference [SMD] = 0.778, 95% confidence interval = 0.284 to 1.272, p = 0.002). Similar results were found after omitting any individual study from meta-analysis, with SMD ranges from 0.318 (95% CI = 0.064 to 0.572, p = 0.014) to 0.914 (95% CI = 0.349 to 1.480, p = 0.002). According to meta-regression analysis, increased mean patients age (slope = − 0.232, 95% CI = − 0.456 to − 0.008, p = 0.042), increased total number of participants (slope = − 0.007, 95% CI = − 0.013 to − 0.0004, p = 0.038), and increased percentage of males (slope = − 6.444, 95% CI = − 10.841 to − 2.047, p = 0.004) were associated with decreased SMD of α-Syn levels across studies. We did not find any significant association between the SMD in α-Syn levels and disease duration, disease severity, and quality of studies. Most of studies applied ELISA assays.


Total plasma α-Syn levels were higher in PD patients than controls. Analytical factors were important limitations.


Biomarker Parkinson’s disease (PD) Meta-analysis Meta-regression Plasma α-Synuclein 





Confidence interval


Cerebrospinal fluid


Enzyme-link immunosorbent assay

H&Y scale

Hoehn and Yahr scale




New Castle-Ottawa scale


Parkinson’s disease


Preferred reporting items for systematic reviews and meta-analyses


Red blood cells


Standardized mean difference


Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

10072_2019_3738_MOESM1_ESM.pdf (47 kb)
ESM 1 (PDF 46 kb)


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Copyright information

© Fondazione Società Italiana di Neurologia 2019

Authors and Affiliations

  1. 1.Neurochemistry laboratory, 1st Department of Neurology and Movement Disorders, Medical School, Aeginition HospitalNational and Kapodistrian University of AthensAthensGreece
  2. 2.Neuroscience laboratory, Center for Basic ResearchBiomedical Research Foundation of the Academy of AthensAthensGreece

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