4.2 Article

Cerebrospinal fluid biomarkers of neuropathologically diagnosed Parkinson's disease subjects

Journal

NEUROLOGICAL RESEARCH
Volume 34, Issue 7, Pages 669-676

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1179/1743132812Y.0000000063

Keywords

2D-DIGE; Cerebrospinal fluid; Parkinson's disease; Proteomics

Funding

  1. Chelsea Therapeutics
  2. Teva Neuroscience
  3. Schering-Plough
  4. Kalaco Scientific
  5. Avid Radiopharmaceuticals
  6. Avid
  7. Bayer
  8. Baxter
  9. BMS
  10. Lilly
  11. GE
  12. Janssen
  13. Celegene
  14. Pfizer
  15. Arizona Parkinson's Disease Consortium [1001]
  16. Brain Donation Program at Banner Sun Health Research Institute
  17. National Institute on Aging [P30 AG19610]
  18. Arizona Department of Health Services [211002]
  19. Arizona Biomedical Research Commission [4001, 0011, 05-901]
  20. Michael J. Fox Foundation for Parkinson's Research

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Objectives: Parkinson's disease (PD) afflicts approximately 1-2% of the population over 50 years of age. No cures or effective modifying treatments exist and clinical diagnosis is currently confounded by a lack of definitive biomarkers. We sought to discover potential biomarkers in the cerebrospinal fluid (CSF) of neuropathologically confirmed PD cases. Methods: We compared postmortem ventricular CSF (V-CSF) from PD and normal control (NC) subjects using two-dimensional difference gel electrophoresis (2D-DIGE). Spots exhibiting a 1.5-fold or greater difference in volume between PD patients and controls were excised from the two-dimensional gels, subjected to tryptic digestion and identification of peptides assigned using mass spectrometric/data bank correlation methods. Results: Employing this strategy six molecules: fibrinogen, transthyretin, apolipoprotein E, clusterin, apolipoprotein A-1, and glutathione-S-transferase-Pi, were found to be different between PD and NC populations. Discussion: These molecules have been implicated in PD pathogenesis. Combining biomarker data from multiple laboratories may create a consensus panel of proteins that may serve as a diagnostic tool for this neurodegenerative disorder.

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