High levels of serum glial fibrillary acidic protein (sGFAP) correlate with disease progression in multiple sclerosis (MS), according to a new study published in the journal Neurology, Neuroimmunology & Neuroinflammation.

This was particularly the case in patients with nonactive disease. Serum neurofilament light chain (sNfL), on the other hand, reflected acute disease activity in patients at high risk of underlying progressive pathology, Tanuja Chitnis, MD, of Harvard Medical School in Boston, Massachusetts, and colleagues noted.

The investigators set out to explore the utility of sNfL and sGFAP as tools to stratify patients with progressive MS in terms of disease progression and activity. In doing so, the researchers analyzed 257 patients with MS from the Comprehensive Longitudinal Investigation of MS at the Brigham and Women’s Hospital natural history study.

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The study includes clinical and magnetic resonance imaging data and serum samples collected over more than 20 years. The analysis included patients with an Expanded Disability Status Scale (EDSS) score of at least 3. 

The researchers looked at sNfL and sGFAP within 6 months of the EDSS score. They grouped patients who further developed 6-month confirmed disability progression as “progressors.” They also stratified the patients into 2 groups based on the presence or absence of new brain and/or spinal cord lesions or relapses as having active or nonactive disease.

The results showed that the levels of sNfL were higher in patients with disease activity in the 2 years before baseline and during the 2-year follow-up period. 

The levels of sGFAP were not higher in patients with active disease. However, higher levels of sGFAP levels were associated with a higher risk of 6-month confirmed disability progression. 

This was not the case for higher levels of sNfL. In fact, the association was even stronger in patients with low sNfL and those with nonactive disease in the 2 years before and after sample collection.

“The use of sNfL and sGFAP has the potential to assess a patient-specific degree of progression, instead of categorizing patients into progressive MS or not, supporting a precision medicine approach for MS,” the study authors concluded. “Thus, sNfL and sGFAP qualify as useful biomarkers for the enrollment of patients with nonactive progressive MS in studies dedicated to stop disease progression.”


Barro C, Healy BC, Liu Y, et al. Serum GFAP, and NfL levels differentiate subsequent progression and disease activity in patients with progressive multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. Published online November 14, 2022. doi:10.1212/NXI.0000000000200052