title: Longitudinal one-year study of levels and stoichiometry of neurofilament heavy and light chain concentrations in CSF in patients with multiple system atrophy.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neuroimmunology, UCL Institute of Neurology, Queen Square, London, UK. a.petzold@ion.ucl.ac.uk
authors.forename: Axel
authors.initials: A
authors.lastname: Petzold
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Thompson
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Keir
authors.forename: Niall
authors.initials: N
authors.lastname: Quinn
authors.forename: Bjorn
authors.initials: B
authors.lastname: Holmberg
authors.forename: Nil
authors.initials: N
authors.lastname: Dizdar
authors.forename: Gregor K
authors.initials: GK
authors.lastname: Wenning
authors.forename: Olivier
authors.initials: O
authors.lastname: Rascol
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tolosa
authors.forename: Lars
authors.initials: L
authors.lastname: Rosengren
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000134:cerebrospinal fluid; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019382:Human Growth Hormone / Q000096:biosynthesis / Q000627:therapeutic use*; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000134:cerebrospinal fluid* / Q000188:drug therapy*; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D016900:Neurofilament Proteins; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D019382:Human Growth Hormone