Neurotoxic tau oligomers after single versus repetitive mild traumatic brain injury

Abstract

Mild traumatic brain injury accounts for the majority of head injuries and has been correlated with neurodegeneration and dementia. While repetitive mild traumatic brain injury is highly correlated to neurodegeneration, the correlation of a single mild traumatic brain injury with neurodegeneration is still unclear. Because tau aggregates are the main form of mild traumatic brain injury induced pathology, toxic forms of tau protein most likely play a role in the development of post-mild traumatic brain injury neurodegeneration. Therefore, it becomes crucial to characterize the properties of soluble tau aggregates in single versus repetitive mild traumatic brain injury. Herein, we isolated tau oligomers from wild-type mice exposed to single or repetitive mild traumatic brain injury and characterized the tau aggregates at functional, biochemical and biophysical levels. We demonstrated that single versus repetitive mild traumatic brain injuries frequencies lead to the formation of different tau oligomeric polymorphisms. These polymorphisms express different long-term potentiation impairment potencies, toxicity potentials, morphologies and strain indicating properties. To our knowledge, this is the first evidence that soluble tau oligomers derived from single versus repetitive mild traumatic brain injuries form distinct polymorphisms that possibly correlate with the risk of neurodegeneration after mild traumatic brain injury.