Defining the Pathophysiological Role of Tau in Experimental TBI
Technical Report,30 Sep 2015,29 Sep 2016
University of Pennsylvania Philadelphia United States
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After traumatic brain injury TBI, the human brain sometimes develops tau pathology partly resembling the hallmark neuropathological features of the tauopathy of Alzheimers disease AD. Although tau has been strongly linked to the pathogenesis of AD, its involvement in the pathophysiology of TBI and its influence on brain structural and functional outcomes are unclear. Here we are critically evaluating three hypotheses i tau exacerbates the neuronal damage and cognitive dysfunction after single and repetitive mild TBI in the acute and chronic post-injury periods ii mild TBI promotes the severity and spread of tau pathology to contribute to development of a chronic neurodegenerative disorder and iii novel biomarkers for neurodegeneration are non-invasive blood measures of brain damage and dysfunction valuable for the diagnosis, prognosis, and theragnosis of mild TBI-triggered brain damage and chronic neurodegenerative disease. At the completion of year 2 of the project, we conclude that in the acute post-injury time period there is no structural, functional, or biomarker evidence for interaction between hippocampal input-specific expression of pathological human tau and either single or repetitive mild TBI. This lack of acute interaction sets the stage for the second phase of the project, examining interactions between tau and mild TBI that may only develop chronically after brain injury, and may contribute to the development of a chronic neurodegenerative condition.
- Anatomy and Physiology
- Medicine and Medical Research