Serum neurofilament light chain in early relapsing remitting MS is increased and correlates with CSF levels and with MRI measures of disease severity
Abstract
Background/objectives: Neurofilament light chain (NfL) levels in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients correlate with the degree of neuronal injury. To date, little is known about NfL concentrations in the serum of relapsing remitting multiple sclerosis (RRMS) patients and their relationship with CSF levels and magnetic resonance imaging (MRI) measures of disease severity. We aimed to validate the quantification of NfL in serum samples of RRMS, as a biofluid source easily accessible for longitudinal studies. Methods: A total of 31 RRMS patients underwent CSF and serum sampling. After a median time of 3.6 years, 19 of these RRMS patients, 10 newly recruited RRMS patients and 18 healthy controls had a 3T MRI and serum sampling. NfL concentrations were determined by electrochemiluminescence immunoassay. Results: NfL levels in serum were highly correlated to levels in CSF ( r = 0.62, p = 0.0002). Concentrations in serum were higher in patients than in controls at baseline ( p = 0.004) and follow-up ( p = 0.0009) and did not change over time ( p = 0.56). Serum NfL levels correlated with white matter (WM) lesion volume ( r = 0.68, p < 0.0001), mean T1 ( r = 0.40, p = 0.034) and T2* relaxation time ( r = 0.49, p = 0.007) and with magnetization transfer ratio in normal appearing WM ( r = −0.41, p = 0.029). Conclusion: CSF and serum NfL levels were highly correlated, and serum concentrations were increased in RRMS. Serum NfL levels correlated with MRI markers of WM disease severity. Our findings further support longitudinal studies of serum NfL as a potential biomarker of on-going disease progression and as a potential surrogate to quantify effects of neuroprotective drugs in clinical trials.
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In mice and in several neurological conditions, including proteopathic neurodegenerative diseases, fluid NfL changes have been associated with brain damage and atrophy.
“Changes of NfL in bodily fluids have been linked to brain damage and brain atrophy in mouse models and multiple neurological disorders including proteopathic neurodegenerative diseases11,13–16.”
From Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease (2019) · cites this paper as [16]
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- Authors
- Kuhle, J., Barro, C., Disanto, G., Mathias, A., Soneson, C., Bonnier, G., Yaldizli, Ö., Regeniter, A., Derfuss, T., Canales, M., Schluep, M., Du Pasquier, R., Krueger, G., & Granziera, C.
- Affiliations
- Neurology, Departments of Medicine, Clinical Research and Biomedicine, University Hospital of Basel, Basel, Switzerland
- University Hospital of Basel (CH)
- Neurocenter of Southern Switzerland, Ospedale Civico, Lugano, Switzerland
- Centre Hospitalier Universitaire Vaudois (CH)
- SIB Swiss Institute of Bioinformatics (CH)
- Laboratory of Neuroimmunology, Center of Research in Neurosciences, Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland/Service of Neurology, Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland
- Advanced Clinical Imaging Technology Group, Siemens Healthcare IM BM PI, Lausanne, Switzerland/Healthcare Sector IM&WS S, Siemens Schweiz AG, Renens, Switzerland
- ORCID
- Venue
- Multiple Sclerosis Journal
- Publisher
- SAGE Publications
- Published
- 2016-07-11
- Volume
- 22
- Issue
- 12
- Pages
- 1550-1559
- ISSN
- 1352-4585 (ISSN-L)
- 1477-0970
- OpenAlex
- W2340550513
- Cited by
- 257
- References
- 36
- Citations by year
- 2026: 16 · 2025: 15 · 2024: 21 · 2023: 26 · 2022: 22 · 2021: 29 · 2020: 35 · 2019: 41 · 2018: 21 · 2017: 24 · 2016: 7
- FWCI
- 28.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Multiple Sclerosis Journal (publishedVersion)
- PubMed (publishedVersion)
- edoc (University of Basel) (submittedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (131914, 154508)
- 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, serum biomarkers, relapsing-remitting multiple sclerosis, cerebrospinal fluid, white matter lesion volume, T1 and T2 relaxation, magnetization transfer ratio, normal-appearing white matter, disease severity, neuroinflammation, neurodegeneration
- MeSH terms
- Adult, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Male, Severity of Illness Index, Neurofilament Proteins, Multiple Sclerosis, Relapsing-Remitting, Young Adult, White Matter
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