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Combination of neurofilament heavy chain and complement C3 as CSF biomarkers for ALS.

Abstract

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disease with an average survival of 3 years from symptom onset. Rapid and conclusive early diagnosis is essential if interventions with disease-modifying therapies are to be successful. Cytoskeletal modification and inflammation are known to occur during the pathogenesis of ALS. We measured levels of cytoskeletal proteins and inflammatory markers in the CSF of ALS, disease controls and healthy subjects. We determined threshold values for each protein that provided the optimal sensitivity and specificity for ALS within a training set, as determined by receiver operating characteristic analysis. Interestingly, the optimal assay was a ratio of the levels for phosphorylated neurofilament heavy chain and complement C3 (pNFH/C3). We next applied this assay to a separate test set of CSF samples to verify our results. Overall, the predictive pNFH/C3 ratio identified ALS with 87.3% sensitivity and 94.6% specificity in a total of 71 ALS subjects, 52 disease control subjects and 40 healthy subjects. In addition, the level of CSF pNFH correlated with survival of ALS patients. We also detected increased pNFH in the plasma of ALS patients and observed a correlation between CSF and plasma pNFH levels within the same subjects. These findings support large-scale prospective biomarker studies to determine the clinical utility of diagnostic and prognostic signatures in ALS.

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  • Authors+Show Affiliations

    ,

    Department of Clinical Neuroscience, King's College London, King's Health Partners, MRC Centre for Neurodegeneration Research, London, UK.

    , , , ,

    Source

    Journal of neurochemistry 117:3 2011 May pg 528-37

    MeSH

    Adult
    Aged
    Amyotrophic Lateral Sclerosis
    Analysis of Variance
    Biological Markers
    C-Reactive Protein
    Complement C3
    Enzyme-Linked Immunosorbent Assay
    Female
    Humans
    Male
    Middle Aged
    Neurofilament Proteins
    ROC Curve
    Statistics as Topic
    tau Proteins

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21418221