Subacute plasma neurofilament light predicts neurodegeneration after moderate‐severe traumatic brain injury

Background TBI is an environmental risk factor for the development of dementia. Axonal injury is thought be a significant determinant of clinical outcomes post‐injury, which can now be assessed using novel techniques such as fluid biomarkers including plasma neurofilament light and advanced MRI assessment. Method BIO‐AX‐TBI (Developing and Validating Blood and Imaging BIOmarkers of AXonal Injury Following Traumatic Brain Injury, NCT03534154) is a multi‐centre cohort study of patients after acute moderate‐severe TBI. Patients admitted to major trauma units underwent baseline clinical assessment, serial blood biomarker and MRI over one year, with detailed outcome ascertainment. Blood concentrations of neurofilament light (NFL), total‐tau, S100‐B, ubiquitin carboxy‐terminal hydrolase L1 (UCHL1) and glial fibrillary acidic protein (GFAP) were quantified. Result 197 patients after TBI had acute blood biomarker assessment with clinical outcomes ascertained at 6 and 12 months. 95 healthy participants with imaging and blood biomarker workup were assessed, alongside 28 healthy controls with longitudinal neuroimaging and 24 trauma patients with extracranial injuries (non‐TBI trauma, ‘NTT’). TBI patients had significant elevations of blood biomarkers including NfL and tau compared with controls and NTTs. Diffusion tensor imaging (DTI) showed reduced fractional anisotropy in TBI patients, which remained abnormal into the chronic phase and correlated with subacute NFL. Grey matter atrophy rates were elevated in the first 6 months post injury and correlated with peak plasma tau levels, which additionally predicted cognitive performance. Abnormal chronic (6‐12) month white matter atrophy, particularly of the right internal capsule/posterior thalamic radiation, was predicted by subacute plasma NFL, which furthermore predicted functional outcome. Conclusion In this longitudinal investigation, subacute plasma NFL was highly sensitive to axonal injury after TBI, predicted functional outcome at 6 and 12 months and predicted accelerated white matter atrophy in the chronic phase. Early plasma tau predicted grey matter atrophy post‐injury and 12 month cognitive function. Plasma NFL and tau appear to be a valuable non‐invasive means to diagnose significant injuries and identify those patients at high risk of chronic neurodegeneration, which may inform recruitment into clinical trials of anti‐neurodegenerative therapies in future.