In healthy neurons, tau is enriched in axons and promotes microtubule (MT) stabilization. It has been postulated that the sequestration of tau into insoluble inclusions results in disruption of normal tau function, which could alter MT stability and fast axonal transport (FAT). An approach to compensate for tau loss-of-function would be to use molecules that stabilize MTs.  Recently the authors identified epothilone D (EpoD) as a preferred MT-stabilizing compound for the potential treatment of tauopathies. The authors tested this hypothesis in a preventative study in which EpoD was administered weekly for 3 months to young PS19 tau Tg mice that initially lacked significant tau pathology. EpoD largely prevented the axonal MT loss and dystrophy, as well as spatial learning deficits, which manifested as these mice developed forebrain tau pathology with age. In the current study the authors test the therapeutic hypothesis that EpoD is efficacious in a prophylactic study- that is in PS19 Tg mice with established tau pathology.  EpoD treatment resulted in significant improvements of MT density, axonal integrity, FAT, and cognitive performance, without the onset of side effects. Moreover, EpoD treatment reduced hippocampal neuron and axon loss. Thus, EpoD safely corrected axonal defects in an interventional mouse model of AD-like tauopathy, suggesting that this agent has potential for the treatment of human tauopathies.