Proteomic Changes of Neurodegenerative and Inflammatory Plasma Biomarkers Following Traumatic Brain Injury

Our objective was to determine if relative concentrations of neurodegenerative and inflammatory biomarkers differed between traumatic brain injury (TBI) and age-matched controls. Among individuals with TBI, we sought to evaluate differences in biomarker expression by injury severity, investigate changes in biomarkers over the first 2 weeks post-injury, and assess associations with functional outcome. Plasma samples from 126 individuals with TBI were collected at day 1 (n = 105) and 2 weeks (n = 67) post-injury, and 34 healthy controls had a single blood draw. TBI severity was defined using the Glasgow Coma Scale (GCS). The Alamar NULISAseq™ CNS Panel was used to obtain expression levels of 122 different proteins associated with neurodegenerative and/or inflammatory processes. Protein levels were compared between groups using adjusted differential expression analysis. Principal component (PC) analysis was performed, and associations between PCs and functional outcome (Glasgow Outcome Scale-Extended, score 7-8 vs. 1-6) were evaluated using adjusted logistic regression. Participants were a median age of 33 years. Compared with controls, day-1 post-injury samples had 17 upregulated and 10 downregulated proteins, with glial fibrillary acidic protein (GFAP), serum amyloid A1, and interleukin-6 showing the greatest increased expression in TBI. At 2 weeks post-injury, 3 proteins were elevated compared with controls (neurofilament light, neurofilament heavy, GFAP) and no proteins were downregulated. When stratified by TBI severity, there were 15 upregulated day-1 post-injury proteins in individuals presenting with GCS 3-12 compared with GCS 13-15. In PC analysis, the first 4 PCs accounted for a total of 45.7% of the variance. Among individuals with TBI, PC2 was associated with higher odds of better 2-week functional outcome (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.02-1.43) and PC3 was associated with lower odds of better 2-week (OR = 0.82, 95% CI = 0.67-0.98) and 6-month (OR = 0.79, 95% CI = 0.63-0.96) functional outcome. In conclusion, our results suggest that proteins of neurodegeneration, synaptogenesis, angiogenesis, and chemokines are associated with TBI outcomes, providing mechanistic insights.