Parkinson‘s Disease: Diagnostic Relevance of Elevated Levels of Soluble α-Synuclein Oligomers In Cerebrospinal Fluid

Abstract

Evaluation of: Tokuda T, Qureshi MM, Ardah MT et al.: Detection of elevated levels of α-synuclein oligomers in CSF from patients with Parkinson disease. Neurology 75, 1766–1772 (2010). This study measured the cerebrospinal fluid (CSF) levels of total and oligomeric α-synuclein (the principal component of Lewy bodies and Lewy neuritis and is characteristic of Lewy body dementias, including Parkinson’s disease [PD]). The authors used quantitative ELISA assays to detect these two types of α-synuclein in PD and control groups, as well as α-synuclein oligomers in PD, progressive supranuclear palsy (PSP), Alzheimer’s disease (AD) and control subjects. All patients fulfilled the well-established clinical criteria for AD, PD and PSP. The PD group had highly elevated α-synuclein oligomers in relation to those detected in the control group (p < 0.0001; sensitivity 75% and specificity 87.5%; area under the curve of 0.859). Greater sensitivity and specificity (89.3 and 90.6%, respectively), with an area under the curve of 0.948, was obtained when the CSF oligomers:total α-synuclein ratio was used. The CSF α-synuclein oligomers and ratio measures were not influenced by age, disease duration and/or clinical symptomatology, including dementia and motor disability in the PD subjects. Interestingly, subjects with mild and early PD had significantly higher α-synuclein oligomer levels and ratios compared with control subjects. In the accompanying cross-sectional study, the CSF α-synuclein oligomer measures were significantly elevated in PD in comparison with AD (p < 0.001), PSP (p < 0.05) and control subjects (p < 0.05). The increased levels of CSF α-synuclein oligomers, even in patients with mild and early PD, suggest their potential use in diagnosing even presymptomatic PD. However, further work is now needed to establish whether these α-synuclein measures can differentiate PD from other α-synucleinopathies (e.g., dementia with Lewy bodies, multiple system atrophy, neurodegeneration with brain iron accumulation), as well as neurological diseases characterized by Parkinsonism but not α-synuclein aggregates (so-called ‘non-α-synucleinopathies’, including a number of taupathies characterized by Parkinsonism [e.g., PSP, corticobasal degeneration, frontotemporal dementia and Parkinsonism linked to chromosome 17 or dementia pugilistica]).