Elevated Serum GFAP Predicts MS-Associated Diffuse White Matter Damage

Investigators sought to better understand the pathological correlates associated with increased serum GFAP in the normal appearing white matter of patients with multiple sclerosis.

Increased serum glial fibrillary acidic protein (GFAP) levels are associated with measurable microdamage in the normal appearing white matter (NAWM) of patients with multiple sclerosis (MS), suggesting that GFAP could be used as a biomarker for pathology-related astrocytopathy in MS, according to study results published in Multiple Sclerosis and Related Disorders.

In this study, 62 patients with MS (median age, 49.2 years) with relapsing remitting (n=39) or secondary progressive (n=23) disease underwent diffusion tension imaging (DTI) and magnetic resonance imaging (MRI), as well as blood sampling for GFAP determination by single molecule array. A total of 10 healthy controls were also recruited for this study.

Study researchers determined mean fractional anisotropy (FA) as well as mean (MD), axial (AD), and radial (RD) diffusivities within the entire NAWM, in addition to 6 segmented regions of NAWM. They used Spearman correlation analysis to evaluate the relationship between DTI parameters and GFAP levels.

Increased levels of GFAP were associated with reduced FA values within the entire NAWM (P =.03) as well as within the frontal (P =.02), temporal (P =.041), and cingulate (P =.034) NAWM. Additionally, increased GFAP levels were linked to increased MD and RD within the frontal NAWM (P =.046 for both). After adjusting for confounding variables, elevated GFAP was also associated with decreased FA in frontal (P =.045) and cingulate NAWM (P =.025). Findings also indicated that higher GFAP was linked to more neuroaxonal damage that caused disease progression.

Limitations of this study included the small sample size as well as the inclusion of participants from a single center.

The study researchers concluded that their study “supports the use of serum GFAP as a biomarker for MS-disease associated astrocytopathy and diffuse white matter damage. In the future simultaneous detection of a combination of biomarkers may provide important information about the distinct aspects of the CNS-related pathology of MS in the clinical follow-up of the patients.”


Saraste M, Bezukladova S, Matilainen M, et al. Increased serum glial fibrillary acidic protein associates with microstructural white matter damage in multiple sclerosis: GFAP and DTI. Mult Scler Relat Disord. Published online February 1, 2021. doi:10.1016/j.msard.2021.102810