Increases of Plasma Levels of Glial Fibrillary Acidic Protein, Tau, and Amyloid β up to 90 Days after Traumatic Brain Injury

Abstract

Glial fibrillary acidic protein (GFAP), microtubule-associated protein tau, and amyloid b peptide (Ab42) have been proposed as diagnostic and prognostic biomarkers in traumatic brain injury (TBI). Single molecule array (Simoa) is a novel technology that employs highly sensitive immunoassays for accurate measurements of candidate biomarkers found at low concentration in biological fluids. Our objective was to trace the trajectory of tau, GFAP, and Ab42 levels in plasma from the acute through subacute stages after TBI, compared with controls. Samples from 34 TBI subjects enrolled in the Citicoline Brain Injury Treatment Trial (COBRIT) were studied. Injury severity was assessed by Glasgow Coma Scale (GCS) and admission CT. Glasgow Outcome Scale Extended (GOSE) was assessed 6 months after injury. Plasma was collected within 24 h (Day 0), and 30 and 90 days after the TBI. Plasma collected from 69 healthy volunteers was used for comparison. At every time point, increases were noted in plasma GFAP ( p < 0.0001 for all comparisons), tau ( p < 0.0001, p < 0.0001, and p = 0.0044, at Days 0, 30, and 90, respectively), and Ab42 ( p < 0.001, p < 0.0001, and p = 0.0203, respectively) in TBI cases compared with controls. The levels were maximal at Day 0 for GFAP and tau and at Day 30 for Ab42. Area under curve (AUC) analyses for Day 0 GFAP and tau were excellent for discrimination of complicated mild TBI (cmTBI) from controls (0.936 and 0.901, correspondingly). Discriminant component analysis (DCA) for all three biomarkers at Days 0 and 30 differentiated controls from cmTBI (91.1% and 89.7% correctly classified, at each time point). Duration of post-traumatic amnesia (PTA) correlated weakly with tau levels at 30 days (Spearman's r = 0.40; 95% CI 0.0003-0.60, p = 0.044). The Marshall CT Grade on admission correlated weakly with Day 30 tau levels (Spearman's r = 0.41; 95% CI 0.04-0.68, p = 0.027). Day 30 Ab42 correlated with GOSE (standardized b -0.486, p = 0.042). GFAP, tau and Ab42 were increased up to 90 days after TBI compared with controls. Total tau levels correlated with clinical and radiological variables of TBI severity. Plasma Ab42 correlated with clinical outcome. Combination of all three biomarkers at Days 0 and 30 can be used to differentiate controls from cmTBI populations, and may be useful as biomarkers of TBI in both acute and subacute phases.

An investigation of neuroinjury biomarkers after sport-related concussion: from the subacute phase to clinical recovery

“…The discrepancy between the current studies' findings and those of Nesilus and colleagues are unclear, warranting future research on the potential dysregulation of plasma T-tau chronically after brain injury. Understanding the relationship between peripheral blood T-tau levels and axonal injury or the accumulation of tau in the brain is important, as peripheral tau has been linked to chronic neurodegenerative disorders such as chronic traumatic encephalopathy and Alzheimer's disease (42,47,(50)(51)(52)(53)(54).…”

The current state of biomarkers of mild traumatic brain injury

“…GFAP levels in CNS have been suggested to improve TBI outcome prediction models and may be able to serve as a marker of intracranial injury (67,68). In fact, GFAP in CSF has been reported to have higher diagnostic accuracy than S100B (69) and was recently shown to have excellent accuracy in differentiating mTBI patients from controls (70). While the best candidate biomarker for mTBI remains to be determined, GFAP does have this clear advantage over S100B.…”

Fluid Biomarkers of Traumatic Brain Injury and Intended Context of Use

“…For example, plasma tau is measurable by Simoa, which showed an increase of the protein in hockey players after concussion and in military personnel who sustained TBIs [74]. A recent study using Simoa showed increases in plasma tau and Aβ42 levels even up to 90 days after mild and moderate-to-severe TBI [75]. …”