Neurology

Biomarker signatures indicate Aldolase C, neurogranin, and synuclein beta are correlated with concussion history in mild TBI





Introduction

Concussion has been studied with increasing scrutiny in recent years, including evaluation of diagnostic technologies to detect structural damage to the brain. Previous studies in our laboratories using a number of TBI biomarkers have demonstrated the potential of blood biomarkers Neurogranin (NRGN), Oligodendrocyte myelin glycoprotein (OMG), and Synuclein beta (SNCB) as indicators of damage after concussion. This study was designed to evaluate the relationship of blood biomarkers with concussion history.

Methods

ELISA assays were developed to detect Aldolase C (ALDOC), Brain derived neurotrophic factor (BDNF), GFAP, Metallothionein-3 (MT3), NRGN, Neuron specific enolase (NSE), OMG, and SNCB. Serum concentrations were determined in replicate assays. Three cohorts were studied: mild TBI patients (HeadSMART; n = 139, Johns Hopkins University); healthy controls (n = 52, Baylor College of Medicine); and semi-professional football players (n = 31; Ben-Gurion University). Serum biomarker values were analyzed by Spearman's pairwise correlation to identify associations with prior concussion number, age, and years of play. Modeling in logistic regression was used to assess risk of PCS at 3 months.

Results

Prior concussion number was correlated with NRGN (p = 0.58), SNCB (p = 0.42), and ALDOC (p = 0.64) in players during the active season. Post-season, NRGN (p = 0.53) and ALDOC (p = 0.37) remain associated with concussion number. ALDOC and NRGN also correlated during the active season (p = 0.68), and ALDOC levels correlated with OMG (0.66), BDNF (–0.51) and NSE (–0.38). In HeadSMART mild-TBI, NRGN was correlated with ALDOC (p = 0.44), and SNCB and BDNF (p = –0.33), and OMG and NSE (p = –0.33) were weakly correlated. ALDOC, BDNF, GFAP, and OMG were associated with age, including decreasing ALDOC and NRGN with age. Classifier models confirmed the utility of these markers for predicting risk of ongoing symptoms (PCS) after mTBI.

Conclusion

Blood levels of NRGN and SNCB are consistently associated with concussion and have been shown to be useful for mTBI diagnosis. These markers, and ALDOC, are promising biomarkers for further development in sports-related concussion.

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