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Abstract
Background: To date, there is no accepted clinical diagnostic test for Parkinson disease (PD) that is based on biochemical analysis of blood or CSF. The discovery of mutations in the SNCA gene encoding α-synuclein in familial parkinsonism and the accumulation of α-synuclein in the PD brain suggested a critical role for this protein in PD etiology.
Methods: We investigated total and α-synuclein oligomers levels in CSF from patients clinically diagnosed with PD, progressive supranuclear palsy (PSP), or Alzheimer disease (AD), and age-matched controls, using ELISA developed in our laboratory.
Results: The levels of α-synuclein oligomers and oligomers/total-α-synuclein ratio in CSF were higher in the PD group (n = 32; p < 0.0001, Mann-Whitney U test) compared to the control group (n = 28). The area under the receiver operating characteristic curve (AUC) indicated a sensitivity of 75.0% and a specificity of 87.5%, with an AUC of 0.859 for increased CSF α-synuclein oligomers in clinically diagnosed PD cases. However, when the CSF oligomers/total-α-synuclein ratio was analyzed, it provided an even greater sensitivity of 89.3% and specificity of 90.6%, with an AUC of 0.948. In another cross-sectional pilot study, we confirmed that the levels of CSF α-synuclein oligomers were higher in patients with PD (n = 25) compared to patients with PSP (n = 18; p < 0.05) or AD (n = 35; p < 0.001) or control subjects (n = 43; p < 0.05).
Conclusion: Our results demonstrate that levels of α-synuclein oligomers in CSF and the oligomers/total-α-synuclein ratio can be useful biomarkers for diagnosis and early detection of PD.
Footnotes
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Study funding: The laboratory of O.M.E. is supported by the Michael J. Fox Foundation for Parkinson's Research.
-
- AD
- Alzheimer disease
- AUC
- area under the receiver operating characteristic curve
- DC
- disease control
- DLB
- dementia with Lewy bodies
- DSM-IV
- Diagnostic and Statistical Manual of Mental Disorders, 4th edition
- HRP
- horseradish peroxidase
- LB
- Lewy body
- mAb
- monoclonal antibody
- NC
- normal control
- PBS
- phosphate-buffered saline
- PBST
- PBS containing 0.05% Tween 20
- PD
- Parkinson disease
- PSP
- progressive supranuclear palsy
- RLU
- relative luminescence units
- ROC
- receiver operating characteristic.
Editorial, page 1760
Supplemental data at www.neurology.org
- Received September 1, 2009.
- Accepted May 25, 2010.
- Copyright © 2010 by AAN Enterprises, Inc.
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