PDE4D and Alzheimer disease: In our present study, PDE4D knockdown rescued Aβ1–42-induced reduction of BDNF and pCREB/CREB levels in the prefrontal cortex, which were consistent with previous studies that suggested that some PDE4 inhibitors, such as rolipram, increase pCREB/CREB ratio and BDNF levels in the frontal cortex and hippocampus of AD mice (Wimmer et al., 2020).