Alzheimer Disease (AD) is the most prevalent form of dementia, and treatments aiming to counteract its effects are missing. Recently, neurons responsible for memory formation (i.e., engrams cells) have been shown to be impaired in mouse models of AD, but no sustained means to rescue their function, and thereby mnemonic capacities are available to date. While partial cellular reprogramming through induction of the Yamanaka Factors (Oct-4, Sox-2, Klf-4 and c-Myc – OSKM) has recently emerged as a promising tool to counteract the systemic effects of aging, reprogramming of specific cell types or in the context of AD has never been done. Here, we developed the first cell-type specific reprogramming approach with the goal to rejuvenate memory cells in AD. Specifically, we triggered the expression of the reprogramming factors OSK in engram cells that were active during learning either in the hippocampus or in the medial prefrontal cortex, as important areas involved in learning and memory expression, respectively. We observed that reprogrammed neurons exhibited several changes consistent with cellular rejuvenation, including increased levels of heterochromatin and identity markers in a cell-autonomous manner. Further, OSK-directed reprogramming increased the reactivation of engram cells and improved spatial learning and memory retention in AD mice. Similar effects in cellular and cognitive rejuvenation were found upon engram reprogramming during physiological aging. Altogether, our data shows that molecular reprogramming is a promising strategy to counteract the effects of aging and AD in engram function and restore cognition in the brain.