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  • Title: Proteomic studies in the discovery of cerebrospinal fluid biomarkers for amyotrophic lateral sclerosis.
    Author: Barschke P, Oeckl P, Steinacker P, Ludolph A, Otto M.
    Journal: Expert Rev Proteomics; 2017 Sep; 14(9):769-777. PubMed ID: 28799854.
    Abstract:
    Amyotrophic lateral sclerosis (ALS) is a progressive degenerative motor neuron disease, which usually leads to death within a few years. The diagnosis is mainly based on clinical symptoms and there is a need for ALS-specific biomarkers to make an early and precise diagnosis, for development of disease-modifying drugs and to gain new insights into pathophysiology. Areas covered: In the present review, we summarize studies using mass spectrometric (MS) approaches to identify protein alterations in the cerebrospinal fluid (CSF) of ALS patients. In total, we identified 11 studies fulfilling our criteria by searching in the PubMed database using the keywords 'ALS' and 'CSF' combined with 'proteome', 'proteomic', 'mass spectrometry' or 'protein biomarker'. Ten proteins were differently regulated in ALS CSF compared to controls in at least 2 studies. We will discuss the relevance of the identified proteins regarding the frequency of identification, extent of alteration and brain-specificity. Expert commentary: Most of the identified CSF biomarker candidates are irreproducible or mainly blood-derived. We assign the missing success of CSF proteomic studies in biomarker discovery to a lack of sensitivity, unsuitable normalization, low quality assurance and variations originating from sample preparation. These issues must be improved in future proteomic studies in CSF.
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