MDM2 and Alzheimer disease: <i>In vivo</i> cognitive deficits and brain pathology were evaluated in AD model mice using Morris water maze tests and immunofluorescence staining.<h4>Results</h4>Experimental results demonstrated that Aβ1-42 induced apoptosis in neuronal cells, while dexmedetomidine incubation significantly reduced Aβ1-42 elicited ROS generation, activated XIAP, suppressed MDM2 and ameliorated P53 overactivation, thereby effectively preventing neuronal death.