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.
RCT Entities:
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 humangrowth 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.
Authors: Claudia Ditzen; Ning Tang; Archana M Jastorff; Larysa Teplytska; Alexander Yassouridis; Giuseppina Maccarrone; Manfred Uhr; Thomas Bronisch; Christine A Miller; Florian Holsboer; Christoph W Turck Journal: Neuropsychopharmacology Date: 2011-12-14 Impact factor: 7.853
Authors: Thomas E Angel; Jon M Jacobs; Serena S Spudich; Marina A Gritsenko; Dietmar Fuchs; Teri Liegler; Henrik Zetterberg; David G Camp; Richard W Price; Richard D Smith Journal: Clin Proteomics Date: 2012-03-20 Impact factor: 3.988
Authors: Emma L van der Ende; Esther E Bron; Jackie M Poos; Lize C Jiskoot; Jessica L Panman; Janne M Papma; Lieke H Meeter; Elise G P Dopper; Carlo Wilke; Matthis Synofzik; Carolin Heller; Imogen J Swift; Aitana Sogorb-Esteve; Arabella Bouzigues; Barbara Borroni; Raquel Sanchez-Valle; Fermin Moreno; Caroline Graff; Robert Laforce; Daniela Galimberti; Mario Masellis; Maria Carmela Tartaglia; Elizabeth Finger; Rik Vandenberghe; James B Rowe; Alexandre de Mendonça; Fabrizio Tagliavini; Isabel Santana; Simon Ducharme; Christopher R Butler; Alexander Gerhard; Johannes Levin; Adrian Danek; Markus Otto; Yolande A L Pijnenburg; Sandro Sorbi; Henrik Zetterberg; Wiro J Niessen; Jonathan D Rohrer; Stefan Klein; John C van Swieten; Vikram Venkatraghavan; Harro Seelaar Journal: Brain Date: 2022-06-03 Impact factor: 15.255