4.4 Article

Total CSF α-synuclein is lower in de novo Parkinson patients than in healthy subjects

Journal

NEUROSCIENCE LETTERS
Volume 532, Issue -, Pages 44-48

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2012.11.004

Keywords

alpha-Synuclein; De novo; Parkinson disease; Cerebrospinal fluid; ELISA; Biomarker

Categories

Funding

  1. Michael J. Fox Foundation for Parkinson's Research
  2. American Parkinson's Disease Association
  3. Stifterverband fur die Deutsche Wissenschaft
  4. TEVA-Pharma
  5. Desitin
  6. Boehringer Ingelheim
  7. German Parkinson Patient Foundation (DPV)
  8. Parkinson Research Consortium Ottawa
  9. Government of Canada (CRC/CIHR)
  10. Department of Medicine of The Ottawa Hospital
  11. Michael J Fox Foundation for Parkinson's Research

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Several studies demonstrated reduced CSF alpha-synuclein values in patients with advanced Parkinson's disease (PD). Values in drug-naive PD subjects and healthy controls (HC) have not yet been reported. We measured CSF values including alpha-synuclein in a cohort of 78 previously untreated PD patients and 48 HC subjects. Measurements of total alpha-synuclein concentrations were performed using two independently operated immunoassays, i.e., one academia-based and previously validated (ELISA 1), the other industry-based, renewable and commercially available (ELISA 2). Mean values for CSF a-synuclein were significantly lower in de novo PD patients when compared to HC subjects, as demonstrated by both assays (ELISA 1, p = 0.049; ELISA 2, p = 0.005; combined, p = 0.002). Using the renewable ELISA 2, CSF alpha-synuclein concentrations of 1884.31 pg/ml or less showed a sensitivity of 0.91 and a specificity of 0.25 for the diagnosis of Parkinson's disease. The corresponding area-under-the-curve value was 0.65 (confidence interval, 0.554-0.750), which was statistically significant (p = 0.004). Total CSF alpha-synuclein is reduced early in the course of Parkinson's disease, as measured by two independent ELISA platforms at the time of enrolment, and this reduction appears independent from drug treatment. Follow-up investigations will determine the usefulness of CSF alpha-synuclein values as markers of progression in individual subjects. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

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