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

Background: The potential of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) as bio-markers 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.

Automated summary

This study investigated the relationship between serum concentrations of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) and disease activity and severity in progressive multiple sclerosis (MS). The results showed that serum concentrations of NfL and GFAP were higher in progressive MS patients compared to healthy controls, and serum NfL was correlated with the EDSS score. Regression analyses revealed that high serum NfL was independently associated with decreased fractional anisotropy (FA) and increased mean diffusivity (MD) in normal-appearing white matter (NAWM), while high serum GFAP was independently associated with decreased MD in NAWM and decreased MD and increased FA in cortical gray matter (CGM).