A comparative study of CSF neurofilament light and heavy chain protein in MS
Abstract
Background: There is a lack of reliable biomarkers of axonal degeneration. Neurofilaments are promising candidates to fulfil this task. We compared two highly sensitive assays to measure two subunits of the neurofilament protein (neurofilament light (NfL) and neurofilament heavy chain (NfH)). Methods: We evaluated the analytical and clinical performance of the UmanDiagnostics NF-light ® enzyme-linked immunosorbent assay (ELISA) in the cerebrospinal fluid (CSF) of a group of 148 patients with clinically isolated syndrome (CIS) or multiple sclerosis (MS), and 72 controls. We compared our results with referring levels of our previously-developed CSF NfH SMI35 assay. Results: Exposure to room temperature (up to 8 days) or repetitive thawing (up to 4 thaws) did not influence measurement of NfL concentrations. Values of NfL were higher in all disease stages of CIS/MS, in comparison to controls ( p ≤ 0.001). NfL levels correlated with the Expanded Disability Status Scale (EDSS) score in patients with relapsing disease ( r s = 0.31; p = 0.002), spinal cord relapses and with CSF markers of acute inflammation. The ability of NfL to distinguish patients from controls was greater than that of NfH SMI35 in both CIS patients ( p = 0.001) and all MS stages grouped together ( p = 0.035). Conclusions: NfL proved to be a stable protein, an important prerequisite for a reliable biomarker, and the NF-light ® ELISA performed better in discriminating patients from controls, compared with the ECL-NfH SMI35 immunoassay. We confirmed and expanded upon previous findings regarding neurofilaments as quantitative markers of neurodegeneration. Our results further support the role of neurofilaments as a potential surrogate measure for neuroprotective treatment in MS studies.
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Although CSF samples were thawed once more in Munich, earlier evidence found that as many as four freeze-thaw cycles do not substantially alter CSF NfL.
“Thus, CSF samples had one additional freeze–thaw cycle in Munich; however, prior work has indicated no significant effect of up to four freeze–thaw cycles on NfL in CSF43.”
From Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease (2019) · cites this paper as [43]
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- Authors
- Kuhle, J., Plattner, K., Bestwick, J. P., Lindberg, R. L., Ramagopalan, S. V., Norgren, N., Nissim, A., Malaspina, A., Leppert, D., Giovannoni, G., & Kappos, L.
- Affiliations
- Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK
- Queen Mary University of London (GB)
- Centre for Human Genetics (GB)
- UmanDiagnostics, Umeå, Sweden
- University Hospital of Basel (CH)
- ORCID
- Venue
- Multiple Sclerosis Journal
- Publisher
- SAGE Publications
- Published
- 2013-03-25
- Volume
- 19
- Issue
- 12
- Pages
- 1597-1603
- ISSN
- 1352-4585 (ISSN-L)
- 1477-0970
- OpenAlex
- W2142588971
- Cited by
- 155
- References
- 37
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 18 · 2023: 7 · 2022: 11 · 2021: 15 · 2020: 14 · 2019: 16 · 2018: 13 · 2017: 11 · 2016: 10 · 2015: 18 · 2014: 7 · 2013: 3
- FWCI
- 9.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Multiple Sclerosis Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Committee for Treatment and Research in Multiple Sclerosis
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- neurofilament light chain, neurofilament heavy chain, multiple sclerosis, clinically isolated syndrome, cerebrospinal fluid biomarkers, axonal degeneration, neurodegeneration, Expanded Disability Status Scale, protein stability, neuroprotective treatment
- MeSH terms
- Adult, Aged, Disability Evaluation, Enzyme-Linked Immunosorbent Assay, False Positive Reactions, Female, Humans, Immunoassay, Inflammation, Male, Middle Aged, Multiple Sclerosis, Nerve Degeneration, ROC Curve, Reproducibility of Results, Biomarkers, Neurofilament Proteins, Disease Progression
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