Objective To investigate the roles of autophagy and Rab9 in the neuronal degeneration of Alzheimer's disease (AD) using 12-month-old APPswe/PS1dE9 double transgenic mice.Methods Immunofluorescence assay was used to measure the expression of Aβ1-16, LC3B, and Rab9 in brain tissue of the 12-month-old APPswe/PS1dE9 double transgenic mice, and the brain tissue samples from wild-type mice in the same brood matched for age and sex were used as controls. Western blot was used to measure the protein expression of LC3B-I, LC3B-Ⅱ, and Rab9 in brain tissue.Results Abundant senile plaques with "dense cores" were observed in the cortex and hippocampus of the 12-month-old APPswe/PS1dE9 double transgenic mice. Compared with the control group, the 12-month-old APPswe/PS1dE9 double transgenic mice had significantly higher expression of LC3B and LC3B-Ⅱ in the brain (LC3B:0.819±0.034 vs 0.390±0.047, P=0.0005; LC3B-Ⅱ:0.162±0.004 vs 0.0672±0.004, P<0.0001). In the 12-month-old APPswe/PS1dE9 double transgenic mice, Rab9 had a course granular shape and gathered in the perinuclear region of neural cells with a special "half-moon" morphology, which was different from the morphology in the control group; however, there was no significant difference in the expression of Rab9 between the two groups (0.481±0.071 vs 0.508±0.064, P>0.05).Conclusions Increased autophagy induction and dysfunction and/or abnormal distribution of Rab9 are observed in the neuronal degeneration of AD.