Alzheimer's disease (AD) is neuropathologically characterized by the presence of extracellular amyloid plaques and intracellular neurofibrillary tangles. The core of senile plaque is amyloid β-protein (Aβ)， which comes from its precursor —— amyloid β-protein precursor (APP). The pQE-APP_28～123 plasmids was constructed by gene recombination. The APP_28～123 protein was expressed in Escherichia coli and then purified. The purified products were examined for GM1 binding abilities by Western blotting. The effects of GM1 on conformation of APP N-terminus were detected by fluorescence and circular dichroism(CD) techniques. APP_28～123 protein could bind with GM1.The intrinsic fluorescence intensity of APP_28～123 protein in PC/GM1 vesicles or GM1 solution remarkably increased and the fluorescence peak value blue shifted 20 nm. CD results showed that the major secondary structure of APP_28～123 in PBS buffer was α-helix. When APP_28～123 incubated with PC/GM1 vesicles or GM1 solution，the α-helix content increased markedly. These results suggested that GM1 might affect the physiological function of APP and change APP span-membrane process and interfere APP trafficking and internalization by anchoring this molecule on the membrane， which may provide much more substrate for γ-secretase and enhance Aβ generation on the cells.