Objective To study the effects of amyloid-β (Aβ) peptides on the cholinergic synapses in the brain of transgenic Drosophila with Alzheimer's disease (AD).Methods An Aβ40-expressing transgenic Drosophila model of AD (Aβ40 group) and an Aβ42-expressing transgenic Drosophila model of AD (Aβ42 group) were established, and wild-type Drosophila (Canton-S) was used as control group. Avidin-biotin staining and confocal laser scanning microscopy were used to record the morphology of projection neurons. The cholinergic spontaneous postsynaptic currents (sPSCs) and miniature excitatory postsynaptic currents (mEPSCs) of projection neurons were recorded by whole-cell patch clamp technique. The short-term olfactory memory was tested by Pavlovian olfactory learning assay.Results Compared with the control group, the Aβ42 group had significantly decreased frequency and amplitude of sPSCs (P<0.05) and significantly decreased frequency of mEPSCs (P<0.05). The Pavlovian olfactory learning assay showed that the Aβ40 and Aβ42 groups had significantly decreased learning and memory indices compared with the control group (P<0.05 for both).Conclusions The effects of Aβ peptides on cholinergic synaptic transmission suggest a possible mechanism by which Aβ peptides cause cholinergic neuron degeneration and the consequent memory loss.