Abstract: Objective:To explore the effects of 12-week aerobic treadmill exercise on the learning and memory ability, Aβ deposition,neuron apoptosis and autophagy activity in the hippocampus of APP/PS1 mice, and to investigate the biological mechanisms of exercise in preventing alzheimer's disease(AD) from the perspective of autophagy. Methods: C57 BL/6 male mice were randomly divided into wild-type sedentary group(WTC, n=9) and wild-type exercise group(WTE, n=9); APP/PS1 male mice were randomly divided into transgenic sedentary group(ADC, n=9) and transgenic exercise group(ADE, n=9). Mice in WTE and ADE groups completed a treadmill exercise program for 12 weeks from 3 months old. After exercise training, Morris water maze test was conducted to evaluate the learning and memory ability of mice. Immunofluorescence was used to detect the area of Aβ deposition plaque and the fluorescence intensity of LC3 in the hippocampus. The content of soluble Aβ40 and Aβ42 in the hippocampus were detected by ELISA kit. The m RNA expression levels of ULK1, P62, Cathepsin D and Rab7 in the hippocampus were detected by Real-time PCR, and the protein expression levels of Aβ, Bax, Bcl2, caspase 3, ULK1, p-ULK1 ser555, LC3 II/I, P62, Cathepsin D and Rab7 were detected by Western blotting.1). Results: 1) The exercise training reduced the latency time and latency distance(P<0.05), and increased the number of times crossing the platform(P<0.01) and the percentage of platform quadrant time(P<0.05) in APP/PS1 mice; 2) The exercise training reduced the area of Aβ plaque(P<0.01) and the protein expression level of Aβ(P<0.01),and decreased the contents of soluble Aβ40 and Aβ42(P<0.01) in the hippocampus of APP/PS1 mice; 3) The exercise training down-regulated the expression of pro-apoptotic proteins Bax(P<0.01) and caspase3(P<0.05), and up-regulated the expression of anti-apoptotic protein Bcl2(P<0.01);moreover, the Bax/Bcl2 ratio was also down-regulated(P<0.05) in the hippocampus of APP/PS1 mice; 4) The exercise training increased the fluorescence intensity of LC3(P<0.01) and the expression of LC3 II/I(P<0.01),and decreased the m RNA and protein expressions of P62 in the hippocampus of APP/PS1 mice(P<0.01); 5) The exercise training up-regulated the m RNA and protein expressions of autophagy promoter ULK1(P<0.05), and increased the protein expression of pULK1 ser555 in the hippocampus of APP/PS1 mice(P<0.05); 6) The exercise training up-regulated the m RNA and protein expressions of Cathepsin D(P<0.01), and up-regulated the m RNA and protein expressions of Rab7 in the hippocampus of APP/PS1 mice(P<0.01). Conclusion: 12-week aerobic treadmill exercise training can activate the autophagy, and enhance the lysosome degradation function, the autophagosome-lysosome fusion, and the autophagy activity in the hippocampus, and then accelerate the degradation rate of Aβ, and inhibit neuronal apoptosis, which resulting in the improvement of learning and memory ability in APP/PS1 mice.