Tau Oligomers Derived from Traumatic Brain Injury Cause Cognitive Impairment and Accelerate Onset of Pathology in Htau Mice

作者：Julia E. Gerson, Diana L. Castillo‐Carranza, Urmi Sengupta, Riddhi U. Bodani, Donald S. Prough, Douglas S. DeWitt, Bridget E. Hawkins, Rakez Kayed · 发表于：Journal of Neurotrauma · 年份：2016 · DOI：10.1089/neu.2015.4262 · 被引用次数：94 · 研究领域：Traumatic Brain Injury and Neurovascular Disturbances、Traumatic Brain Injury Research、S100 Proteins and Annexins

Tau aggregation is a pathological feature of numerous neurodegenerative disorders and has also been shown to occur under certain conditions of traumatic brain injury (TBI). Currently, no effective treatments exist for the long-term effects of TBI. In some cases, TBI not only induces cognitive changes immediately post-injury, but also leads to increased incidence of neurodegeneration later in life. Growing evidence from our lab and others suggests that the oligomeric forms of tau initiate the onset and spread of neurodegenerative tauopathies. Previously, we have shown increased levels of brain-derived tau oligomers in autopsy samples from patients diagnosed with Alzheimer's disease. We have also shown similar increases in tau oligomers in animal models of neurodegenerative diseases and TBI. In the current study, we evaluated the presence of tau oligomers in blast-induced TBI. To test the direct impact of TBI-derived tau oligomer toxicity, we isolated tau oligomers from brains of rats that underwent either a blast- or a fluid percussion injury-induced TBI. Oligomers were characterized biochemically and morphologically and were then injected into hippocampi of mice overexpressing human tau (Htau). Mice were cognitively evaluated and brains were collected for immunological analysis after testing. We found that tau oligomers form as a result of brain injury in two different models of TBI. Additionally, these oligomers accelerated onset of cognitive deficits when injected into brai...