Phosphodiesterase 7 (PDE7) inhibitors are able to regulate the inflammatory response through cyclic AMP (cAMP) signaling cascade and to modulate neuronal plasticity. Thus, PDE7 inhibitors able to recover the homeostasis of cAMP may interfere at the core of Alzheimer Disease (AD) progression and could play a central role in AD and others neurological disorders therapies. Efficacy of PDE 7 inhibitors in different mice models of CNS diseases including spinal cord injury, stroke, multiple sclerosis and Parkinson disease, has been recently reported. Recently results showed the efficacy of this new class of therapeutic agents in a mouse model of AD. Thus, chronic treatment of APPxPS1 mice with our PDE7 inhibitor, the small quinoline compound named S14, a cell permeable and brain penetrant molecule, shown: (1) significant attenuation in behavioral impairment; (2) increase in neuron survival; (3) decreased brain Ab deposition and (4) decreased tau phosphorylation. These effects are mediated via cAMP/CREB and cAMP/PKA signaling pathway, with subsequently inactivation of GSK-3b. To complete the proof of concept of this new PDE7 inhibitor as drug candidate, efficacy on APPxPS1 mice after oral administration of S14 is pursued. Moreover, the potential enhancement of endogeneous neurogenesis after this S14treatment will be done. Successful accomplish of this project will present PDE7 inhibitors, and specifically S14, not only as innovative disease modifying drug candidates for further development as an effective therapy for AD but also as a completely new avenue to repair the damaged brain.