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
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References
- Neurofilament phosphoforms: surrogate markers for axonal injury, degeneration and loss.J Neurol Sci. 2005; 233: 183-198
- Biological markers in CSF and blood for axonal degeneration in multiple sclerosis.Lancet Neurol. 2005; 4: 32-41
- 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
- Safety and tolerability of growth hormone therapy in multiple system atrophy: a double-blind, placebo-controlled study.Mov Disord. 2007; 22: 1138-1144
- Patients with amyotrophic lateral sclerosis and other neurodegenerative diseases have increased levels of neurofilament protein in CSF.J Neurochem. 1996; 67: 2013-2018
- A specific ELISA for measuring neurofilament heavy chain phosphoforms.J Immunol Methods. 2003; 278: 179-190
- Characterization of mammalian neurofilament triplet proteins. Subunit stoichiometry and morphology of native and reconstituted filaments.J Biol Chem. 1985; 260: 10736-10747
- Comparison of two ELISA methods for measuring levels of the phosphorylated neurofilament heavy chain.J Immunol Methods. 2007; 319: 34-40
- A rapid HPLC method to separate the triplet proteins of neurofilament.J Neurochem. 1987; 49: 1375-1378
- Neurofilament functions in health and disease.Curr Opin Neurobiol. 1999; 9: 554-560
- 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
- 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
- Neurofilament homeostasis and motoneurone degeneration.Bioessays. 2001; 23: 24-33
- 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
Article info
Publication history
Published online: February 05, 2009
Accepted:
December 15,
2008
Received in revised form:
December 9,
2008
Received:
July 28,
2008
Identification
Copyright
© 2008 Elsevier B.V. Published by Elsevier Inc. All rights reserved.