Augmenting Neurogenesis Rescues Memory Impairments in Alzheimer's Disease by Restoring the Engram

It is unknown whether adult-born hippocampal neurons play a role in memory deficits in Alzheimer’s disease (AD). Here we show that significantly less new granule neurons, but a similar number of mature neurons, were recruited into contextual memory engram ensemble in a mouse model of AD compared to wild type. Augmentation of neurogenesis in AD mice increased the number of new neurons recruited into the engram and restored memory. The number of new neurons in the engram significantly correlated with the strength of contextual memory. Chemogenetic inactivation of new neurons following enhanced neurogenesis in AD, reversed mouse performance and diminished memory. Collectively, these observations suggest that new neurons play an integral role in memory engram. Insufficient numbers of new neurons recruited into the engram in AD leads to memory deficits. Augmenting hippocampal neurogenesis restores memory impairments by increasing the number of new neurons incorporated in the memory circuit.