Advertisement
Research Article| Volume 279, ISSUE 1-2, P76-79, April 15, 2009

Longitudinal one-year study of levels and stoichiometry of neurofilament heavy and light chain concentrations in CSF in patients with multiple system atrophy

Published:February 05, 2009DOI:https://doi.org/10.1016/j.jns.2008.12.037

      Abstract

      Background

      Two cerebrospinal fluid (CSF) biomarkers specific for neurodegeneration have recently emerged — the neurofilament light (NfL, 68 kDa) and heavy (NfH, 190–210 kDa) chains. This study investigated whether the CSF NfH and NfL levels or their stoichiometric relationship changed over time in a neuroprotective treatment trial.

      Methods

      Serial CSF samples (n=95) from 42 patients with multiple system atrophy (MSA), half randomized to treatment with recombinant human growth hormone (r-hGH) and the other half to placebo, were collected at baseline, 6 and 12 months. The concentration of CSF NfL and NfH was determined using standard ELISAs.

      Results

      There was no consistent change in the levels of either protein over the 12 month period, or between treatment with active r-hGH versus placebo. The molar stoichiometry of CSF NfL:NfH was 4:1 (R=0.37, p=0.0002) and increased following treatment with r-hGH (p=0.03).

      Conclusion

      These results indicate that CSF levels of both NfL and NfH on their own are not useful markers of disease progression in MSA, at least over a 12-month period. Future work is needed to elucidate whether the CSF stoichiometry and dynamics of Nf subunits in individual patients are a feature of the underlying pathology and of diagnostic or prognostic value.

      Abbreviations:

      CSF (cerebrospinal fluid), MSA (multiple system atrophy), Nf (neurofilament), NfH (neurofilament heavy chain), NfL (neurofilament light chain)

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of the Neurological Sciences
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Petzold A.
        Neurofilament phosphoforms: surrogate markers for axonal injury, degeneration and loss.
        J Neurol Sci. 2005; 233: 183-198
        • Teunissen C.E.
        • Dijkstra C.
        • Polman C.
        Biological markers in CSF and blood for axonal degeneration in multiple sclerosis.
        Lancet Neurol. 2005; 4: 32-41
        • Holmberg B.
        • Rosengren L.
        • Karlsson J.E.
        • Johnels B.
        Increased cerebrospinal fluid levels of neurofilament protein in progressive supranuclear palsy and multiple-system atrophy compared with Parkinson's disease.
        Mov Disord. 1998; 13: 70-77
        • Holmberg B.
        • Johansson J.O.
        • Poewe W.
        • Wenning G.
        • Quinn N.P.
        • Mathias C.
        • et al.
        Safety and tolerability of growth hormone therapy in multiple system atrophy: a double-blind, placebo-controlled study.
        Mov Disord. 2007; 22: 1138-1144
        • Rosengren L.E.
        • Karlsson J.E.
        • Karlsson J.O.
        • Persson L.I.
        • Wikkelso C.
        Patients with amyotrophic lateral sclerosis and other neurodegenerative diseases have increased levels of neurofilament protein in CSF.
        J Neurochem. 1996; 67: 2013-2018
        • Petzold A.
        • Keir G.
        • Green A.J.E.
        • Giovannoni G.
        • Thompson E.J.
        A specific ELISA for measuring neurofilament heavy chain phosphoforms.
        J Immunol Methods. 2003; 278: 179-190
        • Scott D.
        • Smith K.E.
        • O B.J.
        • Brien
        • Angelides K.J.
        Characterization of mammalian neurofilament triplet proteins. Subunit stoichiometry and morphology of native and reconstituted filaments.
        J Biol Chem. 1985; 260: 10736-10747
        • Petzold A.
        • Shaw G.
        Comparison of two ELISA methods for measuring levels of the phosphorylated neurofilament heavy chain.
        J Immunol Methods. 2007; 319: 34-40
        • Karlsson J.E.
        • Rosengren L.E.
        • Haglid K.G.
        A rapid HPLC method to separate the triplet proteins of neurofilament.
        J Neurochem. 1987; 49: 1375-1378
        • Julien J.P.
        Neurofilament functions in health and disease.
        Curr Opin Neurobiol. 1999; 9: 554-560
        • Beaulieu J.M.
        • Jacomy H.
        • Julien J.P.
        Formation of intermediate filament protein aggregates with disparate effects in two transgenic mouse models lacking the neurofilament light subunit.
        J Neurosci. 2000; 20: 5321-5328
        • Meier J.
        • Couillard-Despres S.
        • Jacomy H.
        • Gravel C.
        • Julien J.P.
        Extra neurofilament NF-L subunits rescue motor neuron disease caused by overexpression of the human NF-H gene in mice.
        J Neuropathol Exp Neurol. 1999; 58: 1099-1110
        • Perrone Capano C.
        • Pernas-Alonso R.
        • di Porzio U.
        Neurofilament homeostasis and motoneurone degeneration.
        Bioessays. 2001; 23: 24-33
        • Wong N.K.Y.
        • He B.P.
        • Strong M.J.
        Characterization of neuronal intermediate filament protein expression in cervical spinal motor neurons in sporadic amyotrophic lateral sclerosis (ALS).
        J Neuropathol Exp Neurol. 2000; 59: 972-982