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Research paper
Plasma α-synuclein predicts cognitive decline in Parkinson’s disease
  1. Chin-Hsien Lin1,
  2. Shieh-Yueh Yang2,
  3. Herng-Er Horng3,
  4. Che-Chuan Yang2,
  5. Jen-Jie Chieh3,
  6. Hsin-Hsien Chen2,
  7. Bing-Hsien Liu2,
  8. Ming-Jang Chiu1,4,5
  1. 1 Neurology, National Taiwan University Hospital, Taipei, Taiwan
  2. 2 MagQu Co., Ltd., Taipei, Taiwan
  3. 3 Institute of Electro-optical Science and Technology, National Taiwan Normal University, Taipei, Taiwan
  4. 4 Neurology, College of Medicine, National Taiwan University, Taipei, Taiwan
  5. 5 Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan
  1. Correspondence to Professor Ming-Jang Chiu, Neurology, College of Medicine, National Taiwan University, No. 7, Chung-Shan S. Rd, Taipei 10002, Taiwan; mjchiu{at}


Objective α-Synuclein is critical to the pathogenesis of Parkinson’s disease (PD). Few studies examined the plasma levels of α-synuclein due to the exceptionally low level of α-synuclein in plasma compared with cerebrospinal fluid. We aimed to investigate plasma α-synuclein in patients with PD of different disease severity.

Methods There were total 114 participants, including 80 patients with PD and 34 controls, in the study. Participants received a complete evaluation of motor and non-motor symptoms, including cognitive function. We applied immunomagnetic reduction-based immunoassay to measure plasma levels of α-synuclein.

Results Plasma levels of α-synuclein were significantly higher in patients with PD compared with controls (median: 1.56 pg/mL, 95% CI 1.02 to 1.98 pg/mL vs 0.02 pg/mL, 95% CI 0.01 to 0.03 pg/mL; p<0.0001). Although there was a significant increase in plasma α-synuclein levels in PD patients with a higher Hoehn-Yahr (H-Y) stage, there was no correlation with motor symptom severity, as assessed by Unified Parkinson’s Disease Rating Scale part III scores, after confounders (age, gender, and disease duration) were taken into account. However, plasma α-synuclein levels were significantly higher in PD patients with dementia (PDD) than in PD patients with mild cognitive impairment (PD-MCI) or normal cognition (0.42 pg/mL, (95% CI 0.25 to 0.93) for PD with normal cognition; 1.29 pg/mL (95% CI 0.76 to 1.93) for PD-MCI and 4.09 pg/mL (95% CI 1.99 to 6.19) for PDD, p<0.01) and were negatively correlated with Mini-Mental State Examination scores (R2-adjusted=0.3004, p<0.001), even after confounder adjustment.

Conclusions Our data suggest that plasma α-synuclein level correlates with cognitive decline but not motor severity in patients with PD. Plasma α-synuclein could serve as a surrogate biomarker for patients at risk of cognitive decline.

  • Parkinson’s disease
  • Biomarker
  • α-synuclein
  • cognitive decline
  • dementia

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  • Contributors Study concept and design: CHL and MJC.

    Acquisition of data: CHL, SYY, HEH, CCY, JJC, HHC and BHL.

    Analysis and interpretation of data: CHL, SYY and MJC.

    Drafting of the manuscript: CHL.

    Critical revision of the manuscript for important intellectual content: CHL, SYY and MJC.

    Statistical analysis: CHL.

    Obtained funding: CHL and MJC.

    Study supervision: MJC.

  • Funding The authors are grateful to the National Taiwan University Hospital for their support of this work (NTUH 105-002942).

  • Competing interests None declared.

  • Ethics approval Institutional Review Board of National Taiwan University Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Correction notice Since this notice was first published online figure 1 has been updated.

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