One of the hallmarks of Alzheimer disease (AD) is a loss in hippocampus-dependent episodic memory. Whether this results from a failure in memory storage or retrieval is unknown. In a contextual fear conditioning (CFC) model, transgenic mouse models of early AD have defects in long-term memory (LTM) and show age-dependent spinal loss of dentate gyrus (DG) cells. Optogenetically induced long-term potentiation of DG neurons activated during CFC learning (called engram cells) induced memory retrieval, and reduced spinal loss and LTM deficits, suggesting a possible strategy for reversing memory loss in early AD.