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

Journal article
Authors Axel Petzold
Edward J Thompson
Geoffrey Keir
Niall Quinn
Björn Holmberg
Nil Dizdar
Gregor K Wenning
Olivier Rascol
Eduardo Tolosa
Lars Rosengren
Published in Journal of the neurological sciences
Volume 279
Issue 1-2
Pages 76-9
ISSN 1878-5883
Publication year 2009
Published at Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
Pages 76-9
Language en
Keywords Adult, Aged, Aged, 80 and over, Biological Markers, cerebrospinal fluid, Disease Progression, Enzyme-Linked Immunosorbent Assay, Female, Human Growth Hormone, biosynthesis, therapeutic use, Humans, Linear Models, Longitudinal Studies, Male, Middle Aged, Multiple System Atrophy, cerebrospinal fluid, drug therapy, Neurofilament Proteins, cerebrospinal fluid, Neuroprotective Agents, therapeutic use, Recombinant Proteins, therapeutic use
Subject categories Medical and Health Sciences


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.

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