KCTD20 suppression mitigates excitotoxicity in tauopathy patient organoids.

Excitotoxicity is a major pathologic mechanism in patients with tauopathy and other neurodegenerative diseases. However, the key neurotoxic drivers and the most effective strategies for mitigating these degenerative processes are unclear. Here, we show that glutamate treatment of induced pluripotent stem cell (iPSC)-derived cerebral organoids induces tau oligomerization and neurodegeneration and that these phenotypes are enhanced in organoids derived from tauopathy patients.