Alzheimer's disease (AD) is the most common cause of age-related dementia ‎worldwide. It is a neurodegenerative disease characterized by cerebral plaques ‎containing amyloid-β (Aβ) peptide aggregates, intracellular neurofibrillary tangles ‎‎(NFTs) of hyperphosphorylated tau proteins, and neuroinflammation with subsequent ‎death of neurons and brain tissue damage. There is currently no treatment available for ‎the disease or even to halt its progress. Therefore, targeting the etiologic pathologies ‎finding new agents is a crucial requirement. It is speculated that Aβ-induced ‎downregulation of cyclic adenosine monophosphate (cAMP) response element binding ‎protein (CREB) protein, a biological component essential for learning and memory, ‎causes cognitive impairments in AD. Phosphodiesterase (PDE4) inhibitors have been ‎shown to improve AD manifestations by restoring synaptic function through the ‎activation of the cAMP/PKA-CREB-BDNF signaling cascade. Cilomilast (CILO) is a ‎potent selective inhibitor of PDE4 with anti-inflammatory effect that is currently tested ‎in phase III clinical trials as a possible treatment for chronic obstructive pulmonary ‎disease (COPD). Chlorogenic acid (CGA), is a major polyphenol in Coffea that ‎possesses neuroprotective, anti-inflammatory, and anti-oxidative properties. Augmented ‎PDE4 inhibition may be demonstrated through the co-administration of CGA and CILO, ‎which implies that PDE4 inhibitors may serve as potential neuroprotective molecules.‎