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

170 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Cerebrospinal fluid
Amyotrophic Lateral Sclerosis
Biomarkers
Proteomics
Cerebrospinal Fluid
Cystatin C
Prealbumin
Neuroendocrine Secretory Protein 7B2
Ionization
Mass spectrometry
Desorption
Mass Spectrometry
Lasers
Cerebrospinal Fluid Proteins
Learning algorithms
Neurons
Motor Neurons
Ions
Immunohistochemistry
Learning

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis. / Ranganathan, Srikanth; Williams, Eric; Ganchev, Philip; Gopalakrishnan, Vanathi; Lacomis, David; Urbinelli, Leo; Newhall, Kristyn; Cudkowicz, Merit E.; Brown, Robert H.; Bowser, Robert.

In: Journal of Neurochemistry, Vol. 95, No. 5, 01.12.2005, p. 1461-1471.

Research output: Contribution to journalArticle

Ranganathan, S, Williams, E, Ganchev, P, Gopalakrishnan, V, Lacomis, D, Urbinelli, L, Newhall, K, Cudkowicz, ME, Brown, RH & Bowser, R 2005, 'Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis', Journal of Neurochemistry, vol. 95, no. 5, pp. 1461-1471. https://doi.org/10.1111/j.1471-4159.2005.03478.x
Ranganathan, Srikanth ; Williams, Eric ; Ganchev, Philip ; Gopalakrishnan, Vanathi ; Lacomis, David ; Urbinelli, Leo ; Newhall, Kristyn ; Cudkowicz, Merit E. ; Brown, Robert H. ; Bowser, Robert. / Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis. In: Journal of Neurochemistry. 2005 ; Vol. 95, No. 5. pp. 1461-1471.
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