Increasing evidence indicates that cAMP plays a critical role in microglial phagocytosis and phenotypic transformation,[132, 133] possibly through the modulation of H4R and TGF‐β1 signaling pathways,[80, 134, 135] as TGF‐β1 signaling is essential for microglial phagocytosis[98] and the progression of AD.[98, 136, 137] In non‐small‐cell lung cancer (the most common form of lung cancer), activation of H4R resulted in decreased cAMP levels, which suppressed TGF‐β1/Smad3 signaling. This evidence concerns the gene SMAD3 and Alzheimer disease.