Alzheimer 's disease ( AD ) is a neurodegenerative disease characterized by cognitive decline, and neuroinflammation is a key driver. As an important transcription factor, cAMP response element binding protein ( CREB ) is involved in neuroinflammation, synaptic plasticity and neuronal survival by regulating multiple signaling pathways. This article reviews the biological functions of CREB ( neuroplasticity, etc. ), systematically explains the regulatory mechanisms of CREB-mediated cAMP / PKA, MAPK / ERK, PI3K / AKT and other pathways in AD related to neuroinflammation, and summarizes the research progress of CREB agonists of small molecule drugs, natural compounds and cAMP analogues. The precise regulation of CREB may provide a new strategy for AD treatment and provide a theoretical basis for finding new AD therapeutic targets and drug development. This article reviews the research progress of CREB-mediated neuroinflammation in AD.