The microtubule associated protein tau plays a central role in a range of neurodegenerative diseases. Recent data suggest that traumatic brain injury (TBI) leads to progressive tau aggregation, which has been termed chronic traumatic encephalopathy (CTE). Recent experimental data on the molecular basis of tau aggregation demonstrates that tau can undergo transformation into tau prions that are self- propagating. Tau prions spread throughout the brain, analogous to the prions that cause Creutzfeldt-Jakob disease. Combining these new insights with our recent work on in vivo imaging provides an opportunity to develop novel quantitative models of CTE, and follow the generation and progression of tau prions in the brains of transgenic mice. We propose to use blast-induced TBI to initiate tau prion formation in transgenic mice expressing human tau and a bioluminescent reporter. We will then monitor mice behaviorally and by bioluminescence imaging to follow tau prion progression in vivo, finally we will bioassay the tau prions in a second line of transgenic mice.