Traumatic Brain Injury as a Trigger of Neurodegeneration

Although millions of individuals suffer a traumatic brain injury (TBI) worldwide each year, it is only recently that TBI has been recognized as a major public health problem. Beyond the acute clinical manifestations, there is growing recognition that a single severe TBI (sTBI) or repeated mild TBIs (rTBI) can also induce insidious neurodegenerative processes, which may be associated with early dementia, in particular chronic traumatic encephalopathy (CTE). Identified at autopsy examination in individuals with histories of exposure to sTBI or rTBI, CTE is recognized as a complex pathology featuring both macroscopic and microscopic abnormalities. These include cavum septum pellucidum, brain atrophy and ventricular dilation, together with pathologies in tau, TDP-43, and amyloid-β. However, the establishment and characterization of CTE as a distinct disease entity is in its infancy. Moreover, the relative "dose" of TBI, such as the frequency and severity of injury, associated with risk of CTE remains unknown. As such, there is a clear and pressing need to improve the recognition and diagnosis of CTE and to identify mechanistic links between TBI and chronic neurodegeneration.