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  • Title: Proteome analysis reveals candidate markers of disease progression in amyotrophic lateral sclerosis (ALS).
    Author: Brettschneider J, Lehmensiek V, Mogel H, Pfeifle M, Dorst J, Hendrich C, Ludolph AC, Tumani H.
    Journal: Neurosci Lett; 2010 Jan 01; 468(1):23-7. PubMed ID: 19853641.
    Abstract:
    OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: Fetuin-A and TTR are promising candidate markers for disease progression in ALS that warrant further evaluation on a larger cohort of patients.
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