NfL and GFAP in serum are associated with microstructural brain damage in progressive multiple sclerosis

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C. Ammitzbøll
T. B. Dyrby
L. Börnsen
K. Schreiber
R. Ratzer
J. Romme Christensen
P. Iversen
M. Magyari
H. Lundell
P. E.H. Jensen
Sørensen, Per Soelberg
Siebner, Hartwig Roman
Sellebjerg, Finn Thorup

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.

Originalsprog	Engelsk
Artikelnummer	104854
Tidsskrift	Multiple Sclerosis and Related Disorders
Vol/bind	77
Antal sider	8
ISSN	2211-0348
DOI	https://doi.org/10.1016/j.msard.2023.104854
Status	Udgivet - 2023

Bibliografisk note

Funding Information:
We thank all the patients with MS who contributed to this study. Sussi Larsen, Sascha Gude and Hanne Schmidt from the Danish Research centre for Magnetic Resonance did an excellent job in executing MRI and obtaining data. From the Danish Multiple Sclerosis Center we wish to thank Vibeke Jespersen, Sidsel Nielsen and Joan Pietraszek for the professional handling of patient logistics and care and Ulla Abildtrup for excellent performance of single molecule arrays. This study was supported by grants from the Danish Multiple Sclerosis Society (R308 A19240). The funding source were not involved in any practical parts of the study. H.R.S holds a 5-year professorship in precision medicine at the Faculty of Health Sciences and Medicine, University of Copenhagen which is sponsored by the Lundbeck Foundation (Grant Nr. R186–2015–2138). FS holds a professorship at the Faculty of Health Sciences and Medicine, University of Copenhagen sponsored by the Danish Multiple Sclerosis Society. H.L has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No 804746).

Funding Information:
We thank all the patients with MS who contributed to this study. Sussi Larsen, Sascha Gude and Hanne Schmidt from the Danish Research centre for Magnetic Resonance did an excellent job in executing MRI and obtaining data. From the Danish Multiple Sclerosis Center we wish to thank Vibeke Jespersen, Sidsel Nielsen and Joan Pietraszek for the professional handling of patient logistics and care and Ulla Abildtrup for excellent performance of single molecule arrays. This study was supported by grants from the Danish Multiple Sclerosis Society (R308 A19240). The funding source were not involved in any practical parts of the study. H.R.S holds a 5-year professorship in precision medicine at the Faculty of Health Sciences and Medicine, University of Copenhagen which is sponsored by the Lundbeck Foundation (Grant Nr. R186–2015–2138). FS holds a professorship at the Faculty of Health Sciences and Medicine, University of Copenhagen sponsored by the Danish Multiple Sclerosis Society . H.L has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No 804746).

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