CREB1 and Alzheimer disease: The PDE5 inhibitor sildenafil has powerful anti-AD benefits, reversing cognitive decline (García-Osta et al., 2012). The capacity of PDE5 inhibitors to increase cGMP levels and so interfere with the NO/cGMP/PKG/CREB signaling pathway has led to the concept that PDE5 inhibition could be employed as a viable therapeutic method for the treatment of AD (Zuccarello et al., 2020).