Abstract
Cerebrospinal fluid (CSF) is a promising source of biomarkers in amyotrophic lateral sclerosis (ALS). Using the two-dimensional difference in gel electrophoresis (2-D-DIGE), we compared CSF samples from patients with ALS (n = 14) with those from normal controls (n = 14). Protein spots that showed significant differences between patients and controls were selected for further analysis by MALDI-TOF mass spectrometry. For validation of identified spots western blot analysis and ELISA was performed. We identified 2 proteins that were upregulated and 3 proteins that were down-regulated in CSF in ALS. Of these, two proteins (Zn-alpha-2-glycoprotein and ceruloplasmin precursor protein) have not been reported in CSF of patients with ALS so far. In contrast, several other proteins (transferrin, alpha-1-antitrypsin precursor and beta-2-microglobulin) seem to be unspecifically affected in different neurological diseases and may therefore be of limited value as disease-related biochemical markers in ALS. Further evaluation of the candidate proteins identified here is necessary.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Strong M, Rosenfeld J (2003) Amyotrophic lateral sclerosis: a review of current concepts. Amyotrophic Lateral Scler. Other Motor Neuron Disord 4:136–143
Bruijn LI, Miller TM, Cleveland D (2004) Uraveling the mechanisms involved in motor neuron degeneration in ALS. Annu Rev Neurosci 27:723–749
Bowser R, Cudkowicz M, Kaddurah-Daouk R (2006) Biomarkers for amyotrophic lateral sclerosis. Expert Rev Mol Diagn 6:387–398
Pasinetti GM, Ungar LH, Lange DJ et al (2006) Identification of potential CSF biomarkers in ALS. Neurology 66:1218–1222
Ranganathan S, Williams E, Ganchev P et al (2005) Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis. J Neurochem 95:1461–1471
Brooks BR, Miller RG, Swash M et al (2000) Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotrophic Lateral Scler. Other Motor Neuron Disord 1:293–299
Kleyweg RP, van der Meche FG, Schmitz PI (1999) Interobserver agreement in the assessment of muscle strength and functional abilities in Guillain-Barre syndrome. Muscle Nerve 14:1103–1109
The ALS CNTF treatment study (ACTS) phase I-II Study Group (1996) The amyotrophic lateral sclerosis functional rating scale. Assessment of activities of daily living in patients with amyotrophic lateral sclerosis. Arch Neurol 53:141–147
Lehmensiek V, Sussmuth SD, Brettschneider J et al (2007) Proteome analysis of cerebrospinal fluid in Guillain-Barre syndrome (GBS). J Neuroimmunol 185:190–194
Lehmensiek V, Sussmuth SD, Tauscher G et al (2007) Cerebrospinal fluid proteome in multiple sclerosis. Mult Scler 13:840–849
Rosen DR, Siddique T, Patterson D et al (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362:59–62
Bondar OP, Barnidge DR, Klee EW et al (2007) LC-MS/MS quantification of Zn-alpha2 glycoprotein: a potential serum biomarker for prostate cancer. Clin Chem 53:673–678
Hansson SF, Puchades M, Blennow K et al (2004) Validation of a prefractionation method followed by two-dimensional electrophoresis—Applied to cerebrospinal fluid proteins from frontotemporal dementia patients. Proteome Sci 2:7
Ringholz GM, Appel SH, Bradshaw M et al (2005) Prevalence and pattern of cognitive impairment in sporadic ALS. Neurology 65:586–590
Waggoner DJ, Bartnikas TB, Gitlin JD (1999) The role of copper in neurodegenerative disease. Neurobiol Dis 6:221–230
Deng HX, Hentati A, Trainer JA et al (1993) Amyotrophic lateral sclerosis and structural defects in Cu, Zn superoxide dismutase. Science 261:1047–1051
Dumont D, Noben JP, Raus J et al (2004) Proteomic analysis of cerebrospinal fluid from multiple sclerosis patients. Proteomics 4:2117–2124
Hammack BN, Fung KY, Hunsucker SW et al (2004) Proteomic analysis of multiple sclerosis cerebrospinal fluid. Mult Scler 10:245–260
Anckarsäter R, Vasic N, Jidéus L et al (2007) Cerebrospinal fluid protein reactions during non-neurological surgery. Acta Neurol Scand 115:254–259
Carrette O, Demalte I, Scherl A et al (2003) A panel of cerebrospinal fluid potential biomarkers for the diagnosis of Alzheimer’s disease. Proteomics 3:1486–1494
Acknowledgements
We thank Dagmar Vogel, Refika Aksamija and Christa Ondratschek for their help in preparing our CSF samples. This work was supported by funds of the University of Ulm, Germany.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Brettschneider, J., Mogel, H., Lehmensiek, V. et al. Proteome Analysis of Cerebrospinal Fluid in Amyotrophic Lateral Sclerosis (ALS). Neurochem Res 33, 2358–2363 (2008). https://doi.org/10.1007/s11064-008-9742-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11064-008-9742-5