Longitudinal changes in blood-based biomarkers in chronic moderate to severe traumatic brain injury: preliminary findings

Abstract

Background Little is known about the changes in blood-based biomarkers and their relation to outcome, years after TBI. This prospective study aims to provide preliminary evidence of longitudinal changes blood-based biomarkers that relate to changes in outcome measures and cerebral structure and activity.Methods Eight patients with moderate-to-severe TBI were recruited (7 males, 35 ± 7.6 years old, 5 severe TBI, 17.52 ± 3.84 months post-injury). The following data were evaluated at monthly intervals across 6 time-points: a) Blood-based biomarkers, including GFAP, NSE, S100A12, SDBP145, UCH-L1, T-tau, P-tau, and P-tau/T-tau ratio; b) Magnetic Resonance Imaging (MRI) to evaluate changes in brain structure using FMRIB Software Library (FSL); c) Resting state electroencephalograms (EEG) to evaluate changes in brain function using EEGLAB; and d) Outcome measures to assess cognition, emotion and functional recovery (i.e., MOCA, RBANS, BDI-II and DRS).Results Changes in P-tau levels were found across time [p=0.007]. P-tau was positively related to functional [p<0.001] and cognitive [p=0.006] outcomes, and negatively related to the severity of depression, 6 months later [R=-0.901; p=.006]. P-tau and P-tau/T-tau ratio were also positively correlated to shape change in subcortical areas such as brainstem [T(7)=4.71, p=0.008] and putamen [T(7)=3.25, p = 0.012].Conclusions Our study provides preliminary findings that suggest a relationship between P-tau and the recovery of patients with chronic TBI. Further investigation in a larger cohort is warranted to validate this biomarker and better understand the mechanism of neural recovery in chronic patients.