Role of Fluid Biomarkers and GFAP in Neurodegeneration: Charles Bernick, MD


The neurologist at Cleveland Clinic provided perspective on the reasons to study individuals exposed to repetitive head impacts and the lessons learned about monitoring glial fibrillary acidic protein over time. [WATCH TIME: 4 minutes]

WATCH TIME: 4 minutes

"We’re measuring these GFAP levels in people who are in their mid 30s, 40s, and 50s as opposed to the common group you see in Alzheimer disease, which are in their mid 70s and so on. The application of GFAP may be wider, depending on the kind of groups you’re looking at."

Exposure to repetitive head impacts increases the risk of long-term neurological impairment including chronic traumatic encephalopathy; however, not everyone exposed to RHI will experience neurological decline and among those who do, the onset of symptoms may be several years or decades after exposures. To this point, several in the field are working towards identifying biomarkers that could detect the development of a neurodegenerative process and/or follow progression over time. In recent years, a number of candidates have been studied in traumatic brain injury including neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP).

Recently, investigators published data from the Professional Athletes Brain Health Study, which explored the relationship between blood biomarkers and longitudinal change in cognitive function and regional brain volumes in a sample of active and retired professional boxers and Mixed Martial Arts fighters. MRI regional volumes were extracted, along with plasma levels of NfL, GFAP, phosphorylated tau (p-tau)231, and N-terminal tau. In total, 140 active boxers, 211 active MMA, 69 retired boxers, and 52 controls with no prior exposure to head impacts were included.

Results showed a longitudinal increase of GFAP in retired boxers that was associated with decreasing volumes of multiple cortical and subcortical structures (e.g. hippocampus: B = –1.25; 95% CI, –1.65 to –0.85) and increase in lateral ventricle size (B = 1.75; 95% CI, 1.46-2.04). Furthermore, performance on cognitive domains including memory, processing speed, psychomotor speed, and reaction time declined over time with increasing GFAP (e.g. processing speed: B = –0.04; 95% CI, –0.07 to –0.02; reaction time: B = 0.52; 95% CI, 0.28-0.76). Furthermore, increasing levels of GFAP were correlated with lower thalamic and corpus callosum volumes in active fighters.

To learn more about the origins behind the study and the reasons to observe individuals exposed to repetitive head impacts, NeurologyLive® sat down with trial investigator Charles Bernick, MD. Bernick, a neurologist at Cleveland Clinic, provided thoughts on the study background, what was learned about GFAP, and whether these results have implications for other neurodegenerative disorders.

1. Bernick C, Shan G, Ritter A, et al. Blood biomarkers and neurodegeneration in individuals exposed to repetitive head impacts. Alzheimer’s Research & Therapy. 2023;15:173. doi:10.1186/s13195-023-01310-w
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