Chronic traumatic encephalopathy: clinical‐biomarker correlations and current concepts in pathogenesis

Abstract

BackgroundChronic traumatic encephalopathy (CTE) is a recently revived term used to describe a neurodegenerative process that occurs as a long term complication of repetitive mild traumatic brain injury (TBI). Corsellis provided one of the classic descriptions of CTE in boxers under the name “dementia pugilistica” (DP). Much recent attention has been drawn to the apparent association of CTE with contact sports (football, soccer, hockey) and with frequent battlefield exposure to blast waves generated by improvised explosive devices (IEDs). Recently, a promising serum biomarker has been identified by measurement of serum levels of the neuronal microtubule associated protein tau. New positron emission tomography (PET) ligands (e.g., [18 F] T807) that identify brain tauopathy have been successfully deployed for the in vitro and in vivo detection of presumptive tauopathy in the brains of subjects with clinically probable CTE.MethodsMajor academic and lay publications on DP/CTE were reviewed beginning with the 1928 paper describing the initial use of the term CTE by Martland.ResultsThe major current concepts in the neurological, psychiatric, neuropsychological, neuroimaging, and body fluid biomarker science of DP/CTE have been summarized. Newer achievements, such as serum tau and [18 F] T807 tauopathy imaging, are also introduced and their significance has been explained.ConclusionRecent advances in the science of DP/CTE hold promise for elucidating a long sought accurate determination of the true prevalence of CTE. This information holds potentially important public health implications for estimating the risk of contact sports in inflicting permanent and/or progressive brain damage on children, adolescents, and adults.

Neuroinflammation in animal models of traumatic brain injury

“…Concussion models can be used in either mouse or rat, and can involve either a single or repeated injury (Kondo et al, 2015). Neuroinflammation is invariably evident (Faden and Loane 2015), as assessed by astrocytic/microglial reactivity, and can be accompanied with or without alterations in BBB and elevations in phospho-tau levels, particularly the selective cis phosphor-tau form (Kondo et al, 2015) that is evident in chronic traumatic encephalopathy associated with American footballers and other contact sports following multiple concussive and subconcussive injuries (Turner et al, 2013; Gandy et al, 2014). Such animal models, detailed above, are clearly essential for the screening of new therapies for mild concussive and mild to moderate contusion injuries that represent the most frequent types of TBIs, particularly as recent studies suggest that such injuries may be treatable both immediately following and perhaps long after the insult in relation to the neuroinflammation that accompanies them (Faden and Loane 2015).…”

Sports-related brain injuries: connecting pathology to diagnosis

“…Although a powerful tool for both diagnosing and understanding neurological disease, an ideal diagnostic biomarker must fulfill 3 key criteria. 19,32,39,57,118 First, it must be accessible; for a biomarker to be a viable diagnostic option, it must be easily obtained with minimal risk or discomfort to the patient. Following mTBI, CSF may contain elevated proteins from damaged neurons and neuroglia.…”

A Review of the Effectiveness of Neuroimaging Modalities for the Detection of Traumatic Brain Injury

“…Gandy and colleagues provide a recent review of CTE focusing on the association between pathophysiology and clinical findings. 232 Mitsis and colleagues compared and contrasted two cases that include imaging with […”