Our results show that the upregulation of Rheb(S16H) in hippocampal neurons induces a neuroprotective system, attenuates Aβ production and accumulation, and inhibits the decline of LTP in the hippocampus of 5XFAD mice; further, it appears to inhibit cognitive impairments in this animal model. The gene discussed is RHEB; the disease is Cognitive impairment.