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Proteomic profiling of cerebrospinal fluid to identify diagnostic biomarkers for amyotrophic lateral sclerosis



Proteomic profiling of cerebrospinal fluid to identify diagnostic biomarkers for amyotrophic lateral sclerosis



FASEB Journal 18(4-5): Abst 151 5



Amyotrophic lateral sclerosis (ALS) is a common adult motor neuron disease that chronically and progressively affects motor neurons in the post-central gyrus, brain stem and spinal cord. Recent advances in understanding ALS pathogenesis have not yielded diagnostic biomarkers or any long-term drug interventions. Proteomic technologies are a sensitive and valuable tool to discover biomarkers and novel therapeutic targets. We examined the proteomic profile of cerebrospinal fluid (CSF) from ALS patients and control subjects to identify potential disease specific protein biomarkers. Since the CSF is in intimate contact with motor neurons and glia affected during ALS, this medium likely contains the highest level of protein biomarkers. CSF samples were fractionated and profiled on Ciphergen protein chip arrays using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). We found statistically significant differences in approximately 13% of the protein peak intensities between control and ALS subjects. Furthermore, multivariate analysis using two different computer algorithms identified a series of protein peaks that predicted ALS versus control with high sensitivity and specificity. These protein peaks represent the first biomarker panel for this neurodegenerative disease. Continued investigations will yield the protein identity of each biomarker and the function of each protein in disease pathogenesis.

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Accession: 035581930

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