NfL and GFAP in serum are associated with microstructural brain damage in progressive multiple sclerosis
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Background The potential of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) as biomarkers of disease activity and severity in progressive forms of multiple sclerosis (MS) is unclear. Objective To investigate the relationship between serum concentrations of NfL, GFAP, and magnetic resonance imaging (MRI) in progressive MS. Methods Serum concentrations of NfL and GFAP were measured in 32 healthy controls and 32 patients with progressive MS from whom clinical and MRI data including diffusion tensor imaging (DTI) were obtained during three years of follow-up. Results Serum concentrations of NfL and GFAP at follow-up were higher in progressive MS patients than in healthy controls and serum NfL correlated with the EDSS score. Decreasing fractional anisotropy (FA) in normal-appearing white matter (NAWM) correlated with worsening EDSS scores and higher serum NfL. Higher serum NfL and increasing T2 lesion volume correlated with worsening paced autitory serial addition test scores. In multivariable regression analyses with serum GFAP and NfL as independent factors and DTI measures of NAWM as dependent factors, we showed that high serum NfL at follow-up was independently associated with decreasing FA and increasing MD in NAWM. Moreover, we found that high serum GFAP was independently associated with decreasing MD in NAWM and with decreasing MD and increasing FA in cortical gray matter. Conclusion Serum concentrations of NfL and GFAP are increased in progressive MS and are associated with distinct microstructural changes in NAWM and CGM.
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Most studies of NfL rely on serum.
“Third, the inconsistent use of serum versus plasma further complicates comparisons, as most studies of NfL rely on serum.4,6,9,12–14”
From Establishing demographic-based normative values for neurofilament light chain and glial fibrillary acidic protein in serum and plasma samples (2026) · cites this paper as [6]
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White matter integrity, fiber count, and other fallacies: The do's and don'ts of diffusion MRI
Jones, D. K., Knösche, T. R., & Turner, R. (2013) · NeuroImage · doi:10.1016/j.neuroimage.2012.06.081 · Cited by 2,479 · see citing works
MRI in multiple sclerosis: current status and future prospects
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Wang, C., Zhang, W., Ni, M., Wang, Q., Liu, C., Dai, L., Zhang, M., Shen, Y., & Gao, F. (2025) · Alzheimer's Research & Therapy · doi:10.1186/s13195-025-01773-z · Cited by 11 · see citing works
Borko, T. L., Ritchie, A., Selva, S., Sillau, S., Engebretson, E., Wolf, A. B., Alvarez, E., Gross, R., Gutierrez, E., Corboy, J., et al. (2026) · Multiple Sclerosis Journal – Experimental, Translational and Clinical · doi:10.1177/20552173261466440 · Cited by 1 · see citing works
- Authors
- Ammitzbøll, C., Dyrby, T. B., Börnsen, L., Schreiber, K., Ratzer, R., Romme Christensen, J., Iversen, P., Magyari, M., Lundell, H., Jensen, P. E. H., Sørensen, P. S., Siebner, H. R., & Sellebjerg, F.
- Affiliations
- Copenhagen University Hospital (DK)
- Amager Hospital (DK)
- University of Copenhagen (DK)
- Corresponding author
- Ammitzbøll, C.
- ORCID
- Venue
- Multiple Sclerosis and Related Disorders
- Publisher
- Elsevier BV
- Published
- 2023-09
- Volume
- 77
- Pages
- 104854
- ISSN
- 2211-0348 (ISSN-L)
- OpenAlex
- W4382518368
- Cited by
- 20
- References
- 2
- Citations by year
- 2026: 13 · 2025: 5 · 2024: 2
- FWCI
- 3.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Multiple Sclerosis and Related Disorders (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion)
- Funders
- Lundbeck Foundation (R186-2015-2138)
- Det Sundhedsvidenskabelige Fakultet, Københavns Universitet
- Scleroseforeningen (R308 A19240)
- Horizon 2020 (804746)
- European Research Council
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Keywords
- neurofilament light chain, glial fibrillary acidic protein, progressive multiple sclerosis, serum biomarkers, normal-appearing white matter, white matter microstructure, fractional anisotropy, mean diffusivity, cortical gray matter, T2 lesion volume, Expanded Disability Status Scale, diffusion tensor imaging
- MeSH terms
- Brain, Glial Fibrillary Acidic Protein, Humans, Intermediate Filaments, Multiple Sclerosis, Biomarkers, Multiple Sclerosis, Chronic Progressive, Diffusion Tensor Imaging, Gray Matter
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