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J Neurol Neurosurg Psychiatry. 2017 Oct;88(10):818-824. doi: 10.1136/jnnp-2016-314857. Epub 2017 May 26.

Plasma α-synuclein predicts cognitive decline in Parkinson's disease.

Author information

1
Neurology, National Taiwan University Hospital, Taipei, Taiwan.
2
MagQu Co., Ltd., Taipei, Taiwan.
3
Institute of Electro-optical Science and Technology, National Taiwan Normal University, Taipei, Taiwan.
4
Neurology, College of Medicine, National Taiwan University, Taipei, Taiwan.
5
Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan.

Abstract

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.

KEYWORDS:

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

PMID:
28550072
PMCID:
PMC5629933
DOI:
10.1136/jnnp-2016-314857
[Indexed for MEDLINE]
Free PMC Article

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