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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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“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]
Citations
Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482
Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria
Polman, C. H., Reingold, S. C., Banwell, B., Clanet, M., Cohen, J. A., Filippi, M., Fujihara, K., Havrdova, E., Hutchinson, M., Kappos, L., et al. (2011) · Annals of Neurology · doi:10.1002/ana.22366 · Cited by 9,802
Noseworthy, J. H., Lucchinetti, C. F., Rodriguez, M., & Weinshenker, B. G. (2000) · New England Journal of Medicine · doi:10.1056/nejm200009283431307 · Cited by 3,016
Fit-for-Purpose Method Development and Validation for Successful Biomarker Measurement
Lee, J. W., Devanarayan, V., Barrett, Y. C., WEINER, R. S., Allinson, J. L., Fountain, S. T., Keller, S., Weinryb, I., Green, M., Duan, L., et al. (2006) · Pharmaceutical Research · doi:10.1007/s11095-005-9045-3 · Cited by 771
Neurofilament phosphoforms: Surrogate markers for axonal injury, degeneration and loss
Petzold, A. (2005) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2005.03.015 · Cited by 688
Myelin and iron concentration in the human brain: a quantitative study of MRI contrast
Stüber, C., Morawski, M., Schäfer, A., Labadie, C., Wähnert, M., Leuze, C., Streicher, M., Barapatre, N., Reimann, K., Geyer, S., et al. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2014.02.026 · Cited by 635
Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis
Lu, C.-H., Macdonald-Wallis, C., Gray, E., Pearce, N., Petzold, A., Norgren, N., Giovannoni, G., Fratta, P., Sidle, K., Fish, M., et al. (2015) · Neurology · doi:10.1212/wnl.0000000000001642 · Cited by 563
Increased Neurofilament Light Chain Blood Levels in Neurodegenerative Neurological Diseases
Gaiottino, J., Norgren, N., Dobson, R., Topping, J. H., Nissim, A., Malaspina, A., Bestwick, J. P., Monsch, A. U., Regeniter, A., Lindberg, R. L. P., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0075091 · Cited by 493
Self-citationConcepts of myelin and myelination in neuroradiology.
Barkovich, A. J. (2000) · PubMed Central · Cited by 460
Neurochemical Aftermath of Amateur Boxing
Zetterberg, H., Hietala, M. A., Jonsson, M. A. G., Andreasen, N., Styrud, E., Karlsson, I., Edman, Å., Popa, C., Rasulzada, A., Wahlund, L., et al. (2006) · Archives of Neurology · doi:10.1001/archneur.63.9.1277 · Cited by 366
Proteins in cerebrospinal fluid and blood: Barriers, CSF flow rate and source-related dynamics
Reiber, H. (2003) · Restorative Neurology and Neuroscience · doi:10.3233/rnn-2003-00229 · Cited by 354
Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab
Gunnarsson, M., Malmeström, C., Axelsson, M., Sundström, P., Dahle, C., Vrethem, M., Olsson, T. P., Piehl, F., Norgren, N., Rosengren, L., et al. (2010) · Annals of Neurology · doi:10.1002/ana.22247 · Cited by 346
Neurofilament light protein and glial fibrillary acidic protein as biological markers in MS
Malmeström, C., Haghighi, S., Rosengren, L., Andersen, O., & Lycke, J. (2003) · Neurology · doi:10.1212/01.wnl.0000098880.19793.b6 · Cited by 318
Neurofilament protein in cerebrospinal fluid: a potential marker of activity in multiple sclerosis
Lycke, J., Karlsson, J.-E., Andersen, O., & Rosengren, L. (1998) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.64.3.402 · Cited by 315
Scherling, C. S., Hall, T., Berisha, F., Klepac, K., Karydas, A., Coppola, G., Kramer, J. H., Rabinovici, G., Ahlijanian, M., Miller, B. L., et al. (2014) · Annals of Neurology · doi:10.1002/ana.24052 · Cited by 249
Schmitter, D., Roche, A., Maréchal, B., Ribes, D., Abdulkadir, A., Cuadra, M. B., Daducci, A., Granziera, C., Klöppel, S., Maeder, P. P., et al. (2014) · NeuroImage Clinical · doi:10.1016/j.nicl.2014.11.001 · Cited by 206
Self-citationCombination of CSF N -acetylaspartate and neurofilaments in multiple sclerosis
Teunissen, C. E., Iacobaeus, E., Khademi, M., Brundin, L., Norgren, N., Simmelink, M. J. A., Schepens, M., Bouwman, F. H., Twaalfhoven, H. A. M., Blom, H. J., et al. (2009) · Neurology · doi:10.1212/wnl.0b013e3181a0fe3f · Cited by 205
Serum neurofilament light chain is a biomarker of human spinal cord injury severity and outcome
Kühle, J., Gaiottino, J., Leppert, D., Petzold, A., Bestwick, J., Malaspina, A., Lu, C., Dobson, R., Disanto, G., Norgren, N., et al. (2014) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2013-307454 · Cited by 197
Self-citationNeurofilament light as a prognostic marker in multiple sclerosis
Salzer, J., Svenningsson, A., & Sundström, P. (2010) · Multiple Sclerosis Journal · doi:10.1177/1352458509359725 · Cited by 187
Fingolimod and CSF neurofilament light chain levels in relapsing-remitting multiple sclerosis
Kühle, J., Disanto, G., Lorscheider, J., Stites, T. E., Chen, Y., Dahlke, F., Francis, G., Shrinivasan, A., Radue, E. W., Giovannoni, G., et al. (2015) · Neurology · doi:10.1212/wnl.0000000000001491 · Cited by 176
Self-citationA comparative study of CSF neurofilament light and heavy chain protein in MS
Kuhle, J., Plattner, K., Bestwick, J. P., Lindberg, R. L., Ramagopalan, S. V., Norgren, N., Nissim, A., Malaspina, A., Leppert, D., Giovannoni, G., et al. (2013) · Multiple Sclerosis Journal · doi:10.1177/1352458513482374 · Cited by 155
Serum neurofilament light chain levels are increased in patients with a clinically isolated syndrome
Disanto, G., Adiutori, R., Dobson, R., Martinelli, V., Costa, G. D., Runia, T. F., Evdoshenko, E. P., Thouvenot, É., Trojano, M., Norgren, N., et al. (2015) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2014-309690 · Cited by 141
Self-citationChristensen, J. R., Ratzer, R. L., Börnsen, L. S., Lyksborg, M., Garde, E., Dyrby, T. B., Siebner, H. R., Sørensen, P. S., & Sellebjerg, F. T. (2014) · Neurology · doi:10.1212/wnl.0000000000000361 · Cited by 127
Schlaepfer, W., & Lynch, R. (1977) · The Journal of Cell Biology · doi:10.1083/jcb.74.1.241 · Cited by 126
CSF inflammation and axonal damage are increased and correlate in progressive multiple sclerosis
Christensen, J. R., Börnsen, L. S., Khademi, M., Olsson, T. P., Jensen, P. E., Sørensen, P. S., & Sellebjerg, F. T. (2012) · Multiple Sclerosis Journal · doi:10.1177/1352458512466929 · Cited by 98
CSF neurofilament and N-acetylaspartate related brain changes in clinically isolated syndrome
Khalil, M., Enzinger, C., Langkammer, C., Ropele, S., MADER, A., Trentini, A., Vane, M., Wallner-Blazek, M., Bachmaier, G., Archelos, J.-J., et al. (2012) · Multiple Sclerosis Journal · doi:10.1177/1352458512458010 · Cited by 86
Assessing tissue damage in multiple sclerosis: a biomarker approach
Burman, J., Zetterberg, H., Fransson, M., Loskog, A., Raininko, R., & Fagius, J. (2014) · Acta Neurologica Scandinavica · doi:10.1111/ane.12239 · Cited by 85
CSF Neurofilament Light Chain but not FLT3 Ligand Discriminates Parkinsonian Disorders
Herbert, M. K., Aerts, M. B., Beenes, M., Norgren, N., Esselink, R. A. J., Bloem, B. R., Kuiperij, H. B., & Verbeek, M. M. (2015) · Frontiers in Neurology · doi:10.3389/fneur.2015.00091 · Cited by 79
Advanced MRI unravels the nature of tissue alterations in early multiple sclerosis
Bonnier, G., Roche, A., Romascano, D., Simioni, S., Meskaldji, D. E., Rotzinger, D. C., Lin, Y., Menegaz, G., Schluep, M., Pasquier, R. D., et al. (2014) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.68 · Cited by 79
Self-citationModvig, S., Degn, M., Horwitz, H., Cramer, S. P., Larsson, H. B. W., Wanscher, B., Sellebjerg, F. T., & Frederiksen, J. L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077163 · Cited by 63
Cerebrospinal fluid immunological biomarkers associated with axonal damage in multiple sclerosis
Villar, L. M., Picón, C., Costa‐Frossard, L., Alenda, R., García‐Caldentey, J., Espiño, M., Muriel, A., & Álvarez‐Cermeño, J. C. (2014) · European Journal of Neurology · doi:10.1111/ene.12579 · Cited by 54
Granziera, C., Daducci, A., Simioni, S., Cavassini, M. L., Roche, A., Meskaldji, D. E., Kober, T., Métral, M., Calmy, A., Helms, G., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072547 · Cited by 36
Self-citationThe prognostic value of CSF neurofilaments in multiple sclerosis at 15-year follow-up
Petzold, A. (2015) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2014-309827 · Cited by 33
Romascano, D., Meskaldji, D. E., Bonnier, G., Simioni, S., Rotzinger, D. C., Lin, Y., Menegaz, G., Roche, A., Schluep, M., Pasquier, R. D., et al. (2014) · Human Brain Mapping · doi:10.1002/hbm.22698 · Cited by 32
Self-citationPetzold, A., Tozer, D., & Schmierer, K. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.09.011 · Cited by 31
Tissue Properties from Quantitative MRI
Helms, G. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-397025-1.00297-9 · Cited by 14
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Metadata
- 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 › Clinical Neurology › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Clinical 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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