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.