C9orf72 deficiency contributes to synaptic hyperexcitability and excitotoxicity in frontotemporal dementia through CP‐AMPAR dysregulation

Our findings demonstrate that C9orf72 deficiency drives synaptic hyperexcitability and excitotoxic vulnerability through CP-AMPAR dysregulation, implicating this pathway in the pathophysiology of FTD. At the network level, C9orf72 loss amplifies excitatory signaling, linking synaptic dysfunction to network instability and neuronal degeneration. By identifying CP-AMPARs as central mediators of excitotoxicity, this study highlights a novel therapeutic target for C9orf72-associated dementia and other neurodegenerative diseases characterized by excitatory network dysfunction.