Given the strong link between neuronal excitability and neurodegenerative diseases like Alzheimer’s and Frontotemporal Dementia, a model of a vicious cycle where tau and neuronal excitability feedback on each other either from a tau-first insult (FTD) or neuronal excitability insult (AD) could provide a unifying mechanism explaining tauopathy pathogenesis. This evidence concerns the gene MAPT and tauopathy.