Biomarkers of Neurodegeneration in Multiple Sclerosis

Multiple sclerosis (MS) is characterised by inflammatory demyelination and progressive neuroaxonal injury. Biomarkers that reliably reflect neurodegeneration are vital for prognosis, patient stratification and treatment monitoring. Fluid markers such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), measured in cerebrospinal fluid (CSF) or blood, have emerged as sensitive indicators of axonal damage and astroglial activation. Advances in high‐throughput proteomics and ultrasensitive immunoassays now permit the simultaneous quantification of hundreds of proteins, revealing novel combinations that predict disease course and inform therapeutic decisions. Integration of fluid biomarkers with clinical assessment and imaging is reshaping personalised management of MS, enabling earlier detection of progression and more precise evaluation of reparative processes such as remyelination.

Research from Nature Portfolio

An unbiased proteomic analysis of CSF and plasma using proximity‐extension assays coupled with next‐generation sequencing has identified a panel of proteins—including NfL and chemokines—that predicts short- and long-term disability trajectories with high accuracy. This study demonstrated that lower CSF NfL at disease onset correlates with prolonged remission of activity and that a specific combination of eleven proteins forecasts severity of disability worsening.

Longitudinal measurement of serum NfL within 5 years of symptom onset has been shown to predict disability progression over nearly two decades. Patients with baseline serum NfL below defined cut-offs were significantly less likely to reach advanced disability milestones or convert to progressive MS, supporting NfL as a prognostic marker for long-term outcomes.

Complementary work on serum GFAP has revealed its association with disease phenotype and MRI markers of lesion burden. Elevated GFAP distinguishes progressive from relapsing MS and correlates with white matter lesion load as well as reductions in grey and white matter volumes, suggesting a role for GFAP in monitoring astrocytic response and neurodegeneration.

Biomarkers of Neurodegeneration in Multiple Sclerosis publication trend

The graph below shows the total number of articles in biomarkers of neurodegeneration in multiple sclerosis across all publications each year (not limited to Nature Index journals).

Technical terms

Neurofilament light chain (NfL): A neuron‐specific cytoskeletal protein released into CSF and blood upon axonal injury.

Glial fibrillary acidic protein (GFAP): An intermediate filament protein expressed by astrocytes, indicative of astroglial activation and scarring.

Cerebrospinal fluid (CSF): A clear fluid surrounding the brain and spinal cord, used for direct sampling of central nervous system biomarkers.

Proximity‐extension assay: A high‐sensitivity proteomic technique that uses dual antibody recognition and DNA amplification to quantify multiple proteins simultaneously.

TAM receptor system: A family of receptor tyrosine kinases (Tyro3, Axl, Mer) involved in immune regulation, myelin maintenance and remyelination.

Remyelination: The process by which myelin sheaths are restored around demyelinated axons, crucial for functional recovery in MS.

References

1. Proteomics reveal biomarkers for diagnosis, disease activity and long-term disability outcomes in multiple sclerosis. Nature Communications (2023).
2. Tyro3 and Gas6 are associated with white matter and myelin integrity in multiple sclerosis. Journal of Neuroinflammation (2024).
3. Biomarkers in autoimmune diseases of the central nervous system. Frontiers in Immunology (2023).
4. Serum neurofilament light chain predicts long term clinical outcomes in multiple sclerosis. Scientific Reports (2020).
5. Serum GFAP in multiple sclerosis: correlation with disease type and MRI markers of disease severity. Scientific Reports (2020).