Blood Biomarker Reveals Hidden Disability Progression in Multiple Sclerosis

This progression independent of relapse activity is often subtle and may escape routine evaluation, delaying treatment decisions. Although blood neurofilament light chain (NfL) reflects acute inflammatory injury, a marker for progressive disease has been lacking. New findings suggest that serum glial fibrillary acidic protein (GFAP) may track this hidden progression and treatment response.

At the University of Basel and the Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB) at University Hospital Basel, investigators evaluated GFAP as a circulating biomarker of disease worsening. The study, published in JAMA Neurology on August 3, 2026, examined whether GFAP complements established blood testing for NfL. The work addresses progression independent of relapse activity (PIRA), a driver of disability that is difficult to quantify.

GFAP is a structural protein released by astrocytes when they become activated or injured. In contrast, NfL primarily reflects neuroaxonal damage linked to acute inflammatory activity and relapse risk. The researchers assessed how these markers relate to different biological processes in MS and whether serial measurements can inform longitudinal monitoring.

The team analyzed more than 18,000 blood samples and clinical data from over 2,300 people with MS enrolled in two of the world’s largest long-term MS cohorts in Switzerland and the United States. Using repeated measures, they compared biomarker dynamics with subsequent disability progression and relapse outcomes. The cohort scale and follow-up enabled evaluation of both short- and long‑term associations.

Elevated GFAP levels were associated with increased risk of disability progression in both the near term and over longer horizons. By contrast, NfL predominantly captured inflammatory disease activity and was associated with later relapses. Together, the two blood markers provided a more complete view of MS biology, supporting complementary use in clinical assessment.

Changes in GFAP during therapy also carried prognostic information: individuals whose GFAP declined after initiating treatments intended to slow MS had a lower subsequent risk of disability progression. Repeated GFAP measurements could help track disease course and treatment response over time. According to the publication, the findings confirm earlier observations and substantially strengthen evidence for GFAP as a biomarker of PIRA, bringing it a step closer to clinical implementation.

“One of the key questions for us was whether progression leaves a different biological fingerprint than inflammation. If these processes are biologically distinct, we also need biomarkers that reflect different aspects of the disease rather than expecting a single marker to capture everything,” said Professor Jens Kuhle, University of Basel and the Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB) at University Hospital Basel.

“What was particularly noteworthy was not only that higher GFAP levels were associated with gradual disease progression. Changes in the biomarker during treatment were also associated with patients' later risk of disability progression. This suggests that GFAP may capture more than a snapshot of disease activity and reflect biological processes that influence the future course of the disease,” said Maximilian Einsiedler, one of the first authors of the publication. 

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