J Clin Neurol.  2011 Dec;7(4):215-222. 10.3988/jcn.2011.7.4.215.

Elevated Levels of alpha-Synuclein Oligomer in the Cerebrospinal Fluid of Drug-Naive Patients with Parkinson's Disease

• Park MJ
• Cheon SM
• Bae HR
• Kim SH
• Kim JW

• KMID: 2179007
• DOI: http://doi.org/10.3988/jcn.2011.7.4.215

Abstract

BACKGROUND AND PURPOSE
The detection of alpha-synuclein in the body fluids of patients with synucleinopathy has yielded promising but inconclusive results, in part because of conformational changes of alpha-synuclein in response to environmental conditions. The aim of this study was to determine the feasibility of using alpha-synuclein as a biological marker for Parkinson's disease (PD).
METHODS
Twenty-three drug-naive patients with PD (age 62.4+/-12.7 years, mean+/-SD; 11 males) and 29 age- and sex-matched neurologic control subjects (age 60.1+/-16.2 years; 16 males) were recruited. The levels of oligomeric and total alpha-synuclein in the cerebrospinal fluid (CSF) and plasma were measured using two simultaneous enzyme-linked immunosorbent assays.
RESULTS
The level of alpha-synuclein oligomer in the CSF of PD patients was significantly higher in PD patients than in neurological controls, but other findings (plasma alpha-synuclein oligomer and total alpha-synuclein in CSF and plasma) did not differ significantly between the two groups. When the control subjects were divided into a symptomatic control group (11 patients who complained of parkinsonian symptoms and were diagnosed with hydrocephalus and drug-induced or vascular parkinsonism) and a neurologic control group (10 normal subjects and 8 patients with diabetic ophthalmoplegia), the level of alpha-synuclein oligomer in the CSF was still significantly higher in PD patients than in both of the control subgroups.
CONCLUSIONS
These findings provide further evidence for a pathogenic role of the alpha-synuclein oligomer and suggest that CSF levels of alpha-synuclein oligomer can be a reliable marker for PD.

Keyword

Parkinson's disease; cerebrospinal fluid; alpha-synuclein; enzyme-linked immunosorbent assay

MeSH Terms

alpha-Synuclein
Biomarkers
Body Fluids
Enzyme-Linked Immunosorbent Assay
Humans
Hydrocephalus
Parkinson Disease
Plasma
alpha-Synuclein

Figure

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  Fig. 1 Validation of ELISA methods for total and oligomeric forms of α-synuclein. The conventional ELISA (A) and oligomeric methods (B) were selectively sensitive to monomeric and aggregated α-synuclein, respectively. ELISA: enzyme-linked immunosorbent assay.

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  Fig. 2 Levels of total and oligomeric form of α-synuclein in CSF. Solid and white bars indicate measurements using the oligomeric and conventional methods, respectively. CSF: cerebrospinal fluid, PD: Pakinson's disease.

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  Fig. 3 CSF levels of α-synuclein oligomer. The lower, upper, and bisecting lines correspond to the 25th, and 75th percentiles, and the median, respectively. The whiskers indicate the 5th and 95th percentiles. CSF: cerebrospinal fluid, PD: Pakinson's disease.

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  Fig. 4 Levels of total and oligomeric forms of α-synuclein in the plasma. Solid and white bars indicate measurements using the oligomeric and conventional methods, respectively. PD: Pakinson's disease.

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  Fig. 5 CSF levels of α-synuclein oligomer in the control subgroups. The lower, upper, and bisecting lines correspond to the 25th, and 75th percentiles, and the median, respectively. The whiskers indicated the 5th and 95th percentile. CSF: cerebrospinal fluid, PD: Pakinson's disease, Sx: symptomatic control subjects, Nu: neurologic control subjects, MS: multiple sclerosis patients.

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