Extracellular vesicle concentrations of glial fibrillary acidic protein and neurofilament light measured 1 year after traumatic brain injury

Abstract

Traumatic brain injury (TBI) is linked to long-term symptoms in a sub-set of patients who sustain an injury, but this risk is not universal, leading us and others to question the nature of individual variability in recovery trajectories. Extracellular vesicles (EVs) are a promising, novel avenue to identify blood-based biomarkers for TBI. Here, our aim was to determine if glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) measured 1-year postinjury in EVs could distinguish patients from controls, and whether these biomarkers relate to TBI severity or recovery outcomes. EV GFAP and EV NfL were measured using an ultrasensitive assay in 72 TBI patients and 20 controls. EV GFAP concentrations were elevated in moderate and severe TBI compared to controls (p's < 0.001) and could distinguish controls from moderate (AUC = 0.86) or severe TBI (AUC = 0.88). Increased EV GFAP and EV NfL levels were associated with lower 1-year Glasgow Outcome Scale-Extended (GOS-E) score (p's < 0.05). These findings suggest that blood-derived EV concentrations of GFAP and NfL drawn even 1 year after injury are higher in TBI patients compared to controls, and are related to injury severity and poor recovery outcomes, suggesting that TBIs alter the activity of these biomarkers, likely contributing to individual variability in recovery.

Trial registration: ClinicalTrials.gov NCT00888563.

Figure 1

Biomarker differences in TBI patients compared to controls and across TBI severity. (a) EV GFAP was elevated in modTBI and sTBI compared to controls as well as in sTBI versus mTBI (n = 89). (b) EV NfL showed no significant alterations across TBI severity groups or between TBI severity groups and controls (n = 71). Error bars represent SD, with the middle bar indicating the mean. *p < 0.05, ***p < 0.001, adjusted for multiple comparisons. GFAP glial fibrillary acidic protein, NfL neurofilament light chain, EV extracellular vesicle.

Figure 2

Receiver-operating characteristic curves comparing TBI severities and TBI to control. The diagonal blue line indicates the reference line (AUC = 0.5). GFAP glial fibrillary acidic protein, EV extracellular vesicle.

Figure 3

Correlations between 1 year (a) EV GFAP (N = 68) and (b) EV NfL (N = 59) concentrations and outcomes at 1 year, controlling for age and sex. GOS-E Glasgow Outcome Scale-Extended, GFAP glial fibrillary acidic protein, NfL neurofilament light, EV extracellular vesicle.