Longitudinal one-year study of levels and stoichiometry of neurofilament heavy and light chain concentrations in CSF in patients with multiple system atrophy.
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.
Petzold
Axel
A
Department of Neuroimmunology, UCL Institute of Neurology, Queen Square, London, UK. a.petzold@ion.ucl.ac.uk
Thompson
Edward J
EJ
Keir
Geoffrey
G
Quinn
Niall
N
Holmberg
Bjorn
B
Dizdar
Nil
N
Wenning
Gregor K
GK
Rascol
Olivier
O
Tolosa
Eduardo
E
Rosengren
Lars
L
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
D015415:Biomarkers; D016900:Neurofilament Proteins; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D019382:Human Growth Hormone