Exercise might protect against Alzheimer disease (AD) by promoting neurogenesis and raising the levels of brain-derived neurotrophic factor (BDNF), according to a new study. Previous work has suggested that exercise reduces the risk of AD, but the mechanism underlying this association is unclear. In the new study, Choi et al. found that exercise boosted hippocampal neurogenesis, reduced amyloid-β levels, increased the levels of BDNF and improved memory in a mouse model of AD. Ablation of neurogenesis prevented the beneficial effects of exercise in this model. However, genetic or pharmacological induction of neurogenesis in the absence of exercise failed to improve memory. Only the combination of neurogenesis induction with overexpression of BDNF mimicked the memory improvements elicited by exercise. The results suggest that boosting neurogenesis might protect against AD, but only when the health of the local brain environment is also improved.