56 Nevertheless, no effective PDE4 inhibitors are available for clinical use in AD. PDE8, PDE7, and PDE4 are all cAMP-specific hydrolases, and inhibition of PDE8 can also lead to the preservation of cAMP.57 Besides, our study here showed that the PDE8 inhibitor PF increased cAMP levels and promoted the phosphorylation of PKA and CREB, the downstream molecules of cAMP, in both cell and animal experiments. This evidence concerns the gene CREB1 and Alzheimer disease.