Editors' ChoiceTraumatic Brain Injury

The case for tau

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Science Translational Medicine  31 Jan 2018:
Vol. 10, Issue 426, eaar7523
DOI: 10.1126/scitranslmed.aar7523


Pathology consistent with chronic traumatic encephalopathy was found in postmortem brains of teenagers after concussion and was reproduced in a mouse model of traumatic brain injury.

Chronic traumatic encephalopathy (CTE) describes the chronic psychiatric, emotional, and cognitive consequences of repeated head traumas seen particularly in contact sports athletes and in military veterans. CTE is characterized as a progressive tau protein neurodegenerative disease. However, despite intensified research on the study of CTE and mild traumatic brain injury (TBI), the mechanisms responsible for the association between brain injury and CTE are still poorly understood.

Tagge et al. investigated the relationship between brain injury and CTE using postmortem human brain samples and animal models. In the study, authors first compared postmortem brains from teenage athletes in the acute-subacute period after head injury with brains from age-matched athletes. Brains from head-injured subjects showed astrocytosis, axonopathy, microvascular injury, increased perivascular neuroinflammation, and phosphorylated tau protein. These changes occurred soon after acute TBI in humans and resembled pathophysiological features of CTE. To investigate whether a causal relationship existed between head injury and CTE development, they proceeded to develop a new model of concussion induced by a lateral closed-head impact to awake mice, to produce a transient concussion-like syndrome. The model showed that even after a single injury, phosphorylated tauopathy appears early after injury in cortical axons ipsilateral to the site of injury. Eventually, phosphorylated tauopathy spreads to the contralateral cortex 5.5 months after the injury. Importantly, pathophysiologic findings in this mouse model closely resembled the changes seen in humans. Computer modeling showed that as opposed to blast injury models, the impact injury model imposed intracerebral shear stresses are more likely to be responsible for the concussion like neurobehavioral deficits.

Overall, the study suggests that head injuries trigger an early pathologic process including microvascular changes and tau phosphorylation which resembles CTE. Moreover, the use of human samples, the development of a concussion animal model and a computer model allowed for the understanding of the biomechanical forces causing neuropathological and behavioral concussive symptoms.

Further studies examining the time course of tau pathology after TBI in humans are needed. Longitudinal imaging studies in humans may be the next step to better understand the spatiotemporal dynamics of tau pathology after head injury.

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