To observe the effects of moxa combustion products on learning and memory as well as β-amyloid(Aβ) deposition and cholinergic neurotransmitters in the hippocampus(HPC) and entorhinal cortex(EC) in the amyloid precursor protein(APP)/presenilin 1(PS1) mice and investigate whether moxa combustion products can influence cognitive dysfunctions and the involved pathways.Methods:Thirty-six male 16-week-old APP/PS1 mice were assigned into model,moxa smoke,moxa smoke after olfactory impairment,and essential oil groups(n=9) according to a randomized number table.In addition,9 male C57BL/6 mice of 16 weeks old were used as the normal control group.The olfactory impairment was assessed by the buried food pellet test,and the learning and memory of mice were assessed by the Morris water maze test.The positive expression of Aβ in the HPC and EC was detected by immunofluorescence,and the levels of choline acetyltransferase(ChAT) and acetylcholinesterase(AChE) in the two regions were determined by enzyme-linked immunosorbent assay.Results:Compared with the normal control group,APP/PS1 mice showed increased time to search for food(P<0.05),which indicated the successful modeling of olfactory impairment.Compared with the normal control group,the model and moxa-smoke after olfactory impairment groups showcased prolonged escape latency,shortened time in the target quadrant,and reduced number of crossing platforms.Compared with the model group,the moxa smoke and essential oil groups showed shortened escape latency,increased number of crossing platforms,and prolonged time in the target quadrant(P<0.05).Compared with the moxa-smoke after olfactory impairment and model groups,the essential oil and moxa smoke groups demonstrated down-regulated Aβ expression in the hippocampal CA1 region and medial EC region.Compared with the normal control group,the moxa smoke after olfactory impairment and model groups presented reduced ChAT content and increased AChE content in both HPC and EC.Compared with the model group,the essential oil group and the moxa smoke group had increased ChAT content and decreased AChE content in both regions(P<0.05).Conclusion:The moxa combustion products may reduce Aβ deposition and modulate cholinergic neurotransmitter disruption in HPC and EC via the olfactory pathway to improve cognitive function in APP/PS1 mice.