A - 16 Association Between Elevated GFAP and Acute White Matter Changes Following Sport-Related Concussion

Abstract Purpose Blood-based biomarkers have shown promise for identifying athletes with concussion, though their relationship with other markers of physiological injury has not been definitely established. We examined whether increased acute post-concussion glial fibrillary acidic protein (GFAP) in plasma, as determined at the subject level using reliable change index (RCI), is associated with white matter injury. Method Neuroimaging and biomarker data were prospectively collected from concussed collegiate athletes (N = 86) recruited through the CARE Consortium. Mean diffusivity (MD) was derived from diffusion tensor imaging data. Reliable change in plasma GFAP levels (Quanterix platform) was calculated by dividing the difference between baseline and acute post-injury visits by the standard error of the difference from uninjured controls. Athletes with RCI > 1.65 (95th percentile) were classified as having “elevated” GFAP. Mixed-effects models with random intercepts were used to assess the association between GFAP status (elevated/non-elevated) and MD in the corpus callosum (primary) and additional white matter regions (exploratory), accounting for sex and site. Results Of 86 athletes with concussion, 14 (16%) had elevated GFAP. Increased GFAP was associated with higher MD in the splenium of the corpus callosum (p = 0.016), but not genu or body. No significant associations were found between GFAP elevations and MD in other exploratory white matter regions. Conclusions Acute post-concussion elevations in GFAP identified at the individual level using reliable change reflect mean diffusivity in the splenium of the corpus callosum, suggesting elevations in GFAP reflect more severe white matter injury.