PDE4D and Alzheimer disease: PDE4 inhibitors such as roflumilast, apremilast, and crisaborole have been approved for the treatment of inflammatory airway diseases, psoriatic arthritis, and atopic dermatitis, respectively.53 Furthermore, PDE4 inhibitors such as roflumilast and rolipram can modulate neuroinflammation and drive the endogenous regeneration of neurons and oligodendrocytes, thereby delaying the progression of AD by governing cAMP and its downstream pathways.54,55 The PDE4D inhibitor zatolmilast has demonstrated positive effects in Phase II clinical trials for AD.