Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis

Srikanth Ranganathan, Eric Williams, Philip Ganchev, Vanathi Gopalakrishnan, David Lacomis, Leo Urbinelli, Kristyn Newhall, Merit E. Cudkowicz, Robert H. Brown, Robert Bowser

Research output: Contribution to journalArticle

174 Scopus citations

Abstract

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons. We tested the hypothesis that proteomic analysis will identify protein biomarkers that provide insight into disease pathogenesis and are diagnostically useful. To identify ALS specific biomarkers, we compared the proteomic profile of cerebrospinal fluid (CSF) from ALS and control subjects using surface-enhanced laser desorption/ ionization-time of flight mass spectrometry (SELDI-TOF-MS). We identified 30 mass ion peaks with statistically significant (p < 0.01) differences between control and ALS subjects. Initial analysis with a rule-learning algorithm yielded biomarker panels with diagnostic predictive value as subsequently assessed using an independent set of coded test subjects. Three biomarkers were identified that are either decreased (transthyretin, cystatin C) or increased (carboxy-terminal fragment of neuroendocrine protein 7B2) in ALS CSF. We validated the SELDI-TOF-MS results for transthyretin and cystatin C by immunoblot and immunohistochemistry using commercially available antibodies. These findings identify a panel of CSF protein biomarkers for ALS.

Original languageEnglish (US)
Pages (from-to)1461-1471
Number of pages11
JournalJournal of neurochemistry
Volume95
Issue number5
DOIs
StatePublished - Dec 1 2005

Keywords

  • Amyotrophic lateral sclerosis
  • Cerebrospinal fluid
  • Mass spectrometry
  • Proteomics

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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    Ranganathan, S., Williams, E., Ganchev, P., Gopalakrishnan, V., Lacomis, D., Urbinelli, L., Newhall, K., Cudkowicz, M. E., Brown, R. H., & Bowser, R. (2005). Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis. Journal of neurochemistry, 95(5), 1461-1471. https://doi.org/10.1111/j.1471-4159.2005.03478.x