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Neurosci Lett. 2010 Jan 1;468(1):23-7. doi: 10.1016/j.neulet.2009.10.053. Epub 2009 Oct 22.

Proteome analysis reveals candidate markers of disease progression in amyotrophic lateral sclerosis (ALS).

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Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany.



In amyotrophic lateral sclerosis (ALS) the pathological determinants of disease progression remain poorly understood. We aimed to identify a characteristic CSF protein pattern that could provide new candidate biomarkers of disease progression in ALS.


Using the two-dimensional difference in gel electrophoresis (2-D-DIGE), we compared CSF samples from patients with ALS that showed a rapid progression of disease (ALS-rp, n=9) over a follow-up time of 2 years and from patients with ALS that showed a slow progression of disease over follow-up (ALS-sl, n=9) over the same period. 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 ELISA and nephelometry were performed for two candidate proteins on a second cohort of patients (n=40).


We identified 6 different proteins and their isoforms which were all upregulated in ALS-rp as compared to ALS-sl (heat shock protein1, alpha-1 antitrypsin, fetuin-A precursor, transferrin, transthyretin (TTR), nebulin-related anchoring protein). For Fetuin-A and TTR, our findings could be confirmed by quantitative assay.


Fetuin-A and TTR are promising candidate markers for disease progression in ALS that warrant further evaluation on a larger cohort of patients.

[Indexed for MEDLINE]

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