A Model of Traumatic Brain Injury Oligomerizes Tau in Cortical Organoids and Induces Clinically Relevant Pathologies that Synergize with MAPT Mutation

Traumatic brain injury (TBI) is the most important environmental risk factor for neurodegenerative disease. Tauopathy plays an important role in post-traumatic neurodegeneration. Human-induced pluripotent stem cell (hiPSC)-derived cortical organoids have exciting potential to reveal the influence of genotype on post-traumatic neurodegeneration because they permit manipulation of the genome in a human system.The purpose of this study was to examine how Microtubule associated protein tau (MAPT) mutations influence tau pathology and injury responses following traumatic brain injury (TBI) in a human in vitro model. An isogenic 3D cortical organoid system was established to investigate gene–trauma interactions contributing to neurodegeneration.创伤性脑损伤（Traumatic brain injury, TBI）是引发神经退行性疾病的最关键环境危险因素。tau蛋白病在创伤后神经退行性变过程中发挥重要作用。人类诱导多能干细胞（human-induced pluripotent stem cell, hiPSC）来源的皮层类器官，因其可在人类体系中实现基因组操控，在揭示基因型对创伤后神经退行性变的影响方面具有极具前景的应用潜力。本研究旨在探究人类体外模型中，微管相关蛋白tau（Microtubule associated protein tau, MAPT）突变如何影响创伤性脑损伤（TBI）后的tau病理与损伤应答。本研究构建了同基因三维皮层类器官系统，以探究参与神经退行性变的基因-损伤相互作用。