Preserving cAMP levels by inhibiting PDE can not only ameliorate Aβ-induced neuronal damage but also regulate Aβ generation.63 In this study, the PDE8 inhibitor PF decreased Aβ levels and downregulated the expression of APP and PS1 in APP/PS1 mice, suggesting that inhibiting Aβ generation may also be another mechanism by which PDE8 inhibition exerts favorable effects in AD. This evidence concerns the gene PSEN1 and Alzheimer disease.