Studies suggest that restoration of synaptic failure in AD can be achieved through CREB activation [48], and since CREB activation is coupled to NO/cGMP signaling in the hippocampus [22, 23], we hypothesized that incorporation of a CREB activating moiety would reactivate circuits associated with CREB which are vital to learning and memory [49]. This evidence concerns the gene CREB1 and Alzheimer disease.