Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, The University of Texas Health Science Center at Houston, Houston, Texas.
Department of Neurobiology and Anatomy, The University of Texas Health Science Center at Houston, Houston, Texas.
J Neurotrauma. 2020 Jan 1;37(1):80-92. doi: 10.1089/neu.2018.6348. Epub 2019 Aug 28.
The misfolding and aggregation of tau protein into neurofibrillary tangles is the main underlying hallmark of tauopathies. Most tauopathies have a sporadic origin and can be associated with multiple risk factors. Traumatic brain injury (TBI) has been suggested as a risk factor for tauopathies by triggering disease onset and facilitating its progression. Several studies indicate that TBI seems to be a risk factor to development of Alzheimer disease and chronic traumatic encephalopathy, because there is a relationship of TBI severity and propensity to development of these illnesses. In this study, we evaluated whether moderate to severe TBI can trigger the initial formation of pathological tau that would induce the development of the pathology throughout the brain. To this end, we subjected tau transgenic mice to TBI and assessed tau phosphorylation and aggregation pattern to create a spatial heat map of tau deposition and spreading in the brain. Our results suggest that brain injured tau transgenic mice have an accelerated tau pathology in different brain regions that increases over time compared with sham mice. The appearance of pathological tau occurs in regions distant to the injury area that are connected synaptically, suggesting dissemination of tau aggregates. Overall, this work posits TBI as a risk factor for tauopathies through the induction of tau hyperphosphorylation and aggregation.
tau 蛋白错误折叠和聚集形成神经纤维缠结是 tau 病的主要潜在标志。大多数 tau 病具有散发性起源，可以与多种风险因素相关。创伤性脑损伤（TBI）通过引发疾病发作和促进其进展，被认为是 tau 病的一个风险因素。几项研究表明，TBI 似乎是阿尔茨海默病和慢性创伤性脑病发展的一个风险因素，因为 TBI 的严重程度和发展这些疾病的倾向之间存在关系。在这项研究中，我们评估了中度至重度 TBI 是否会引发病理性 tau 的最初形成，从而导致整个大脑的病理学发展。为此，我们使 tau 转基因小鼠遭受 TBI，并评估 tau 磷酸化和聚集模式，以创建 tau 在大脑中沉积和扩散的空间热图。我们的结果表明，与假手术小鼠相比，脑损伤的 tau 转基因小鼠在不同脑区的 tau 病理学有加速发展，且随时间推移而增加。病理性 tau 的出现发生在与损伤区域相隔较远的、通过突触连接的区域，表明 tau 聚集物的传播。总的来说，这项工作通过诱导 tau 过度磷酸化和聚集，提出 TBI 是 tau 病的一个风险因素。
