The accumulation of amyloid-β peptides (Aβ) is a critical trigger of Alzheimer's disease (AD) pathogenesis. Aβ is derived from sequential proteolysis of amyloid precursor protein by β- and γ-secretases. Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels. Microglia and bone marrow-derived microglia-like (BMDML) cells have Aβ phagocytic function, and nicotinic stimulation promotes microglial Aβ phagocytosis. However, it is not yet known the nicotinic effects on BMDML cells and nAChR subtypes which involve in the promotion of microglial Aβ phagocytosis. We here found that the stimulation of nAChRs promoted Aβ phagocytosis in BMDML cells and α7 nAChR was involved in the promotion of microglial Aβ phagocytosis. In a mouse model of AD, stimulation of α7 nAChR attenuated brain Aβ burden and memory dysfunction. Moreover, α7 nAChR agonist suppressed γ-secretase activity. Results suggests that α7 nAChR subtype is a reasonable drug discovery target in AD, and the stimulation of nAChRs in BMDML cells may be a beneficial option for the development of the cell therapy in AD.