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.
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.
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).
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)
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Published online: February 05, 2009
Accepted: December 15, 2008
Received in revised form: December 9, 2008
Received: July 28, 2008
© 2008 Elsevier B.V. Published by Elsevier Inc. All rights reserved.