Cerebrospinal fluid biomarkers of neuropathologically diagnosed Parkinson's disease subjects

Abstract

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.

Figure 1

A) 2D-DIGE master gel showing spots with 1.5x or greater differences in spot volume. Spots encircled in blue are increased in the PD group and spots encircled in red are decreased in the PD group, relative to the NC cohort. The two spots on the acidic side were likely artifacts and not included in the study. Note that pI and kDa are approximate. B) The spot distribution in PD and NC 2D-DIGE gels. The left Y-axis represents spot frequency and the right Y-axis represents the maximum spot volume of a given pair of spots. The red curve signifies the frequency of distribution of the log volume rations while the blue curve is the normalized model frequency fitted to the spot ratios so that the modal peak is zero. The black vertical lines are set at a 1.5-fold difference in PD/NC spot volume ratio (red spots = decrease in PD; blue spots = increase in PD).