Traumatic Tauopathy
CHAIR
PRESENTERS
DESCRIPTION
Chronic traumatic encephalopathy (CTE) represents a progressive tauopathy associated with repetitive concussive and subconcussive trauma to the head. Clinically, CTE can present with cognitive, behavioral, and/or motorical symptomatology. Pathologically CTE is characterized by the abnormal accumulation of hyperphosphorylated tau in the brain. Currently, post-mortem examination is the only method to definitively diagnose CTE. The ante-mortem diagnosis of CTE can be challenging and is in the differential diagnosis of sport related chronic traumatic brain injury (chronic postconcussion syndrome, chronic neurocognitive impairment) and other tauopathies (e.g. Alzheimer’s disease, frontotemporal dementia, corticobasal degeneration). Sophisticated neuroimaging techniques may be utilized to diagnose other types of neurodegenerative disorders and tau radiotracers for positron emission tomography (PET) scanning are under development. Tau is the major microtubule associated protein of the mature neuron whose function is to modulate the stability of axonal microtubules. Tau is encoded by the MAPT gene on chromosome 17 and is expressed as six molecular isoforms. Post-translational tau phosphorylation is achieved by several protein kinases and the dephosphorylation of tau is accomplished by protein phosphatase 2A (PP2A). Abnormal hyperphosphorylization of tau results in the self-assembly and aggregation of tau and the formation of paired helical filaments and neurofibrillary tangles. Hyperphosphorylated tau also binds to normal tau which theoretically results in a prion-like tau propagation in the brain. It is hypothesized that the trans-synaptic spread of tau pathology involves the release of tau oligomers from dead or dying tangle -bearing neurons to naive neurons in proximity. Tau pathology may represent a therapeutic target for tauopathies. The inhibition of tau hyperphosphorylation by the inhibition of tau kinases or the upregulation of PP2A represents a potential therapeutic approach. Other investigational therapeutic approaches include inhibition of tau aggregation and the clearance of pathological tau.
LEARNING OBJECTIVES
- Differentiate between the various neurobehavioral conditions which can present as a sport related chronic traumatic brain injury and recognize the clinicopathological characteristics of chronic traumatic encephalopathy (CTE).
- Describe the normal physiological functions of tau and the pathological consequences of tau hyperphosphorylation, oligomerization, deposition and propagation.
- Identify investigational and novel anti-tau therapeutics which can potentially mitigate tau neurotoxicity.
