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

Background and Purpose The detection of alpha-synuelein 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 a-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. J Clin Neurol 2011;7:215-222