Abstract: Objective: The present study aims to observe the changes in Aβ deposition and estrogen receptor levels in the hippocampal tissue of female APP/PS1 mice with Alzheimer's disease (AD) after ovariectomy (ovx) at different ages. Method: 3-month-old APP/PS1 female mice were divided into 3 groups, with 20 mice in each group. 10 mice in each group were treated with bilateral ovarian resection via abdominal surgery as the model group. 10 mice in the control group (sham group) were treated with only equivalent volume fat removed from the corresponding area during surgery as the control group (sham group). Feed APP/PS1 mice at different ages for 3 months, 4 months, and 5 months as the 6-month, 7-month, and 8-month age groups. Evaluate the cognitive function of APP/PS1 mice at different ages using Morris water maze. Observe the morphological changes of intracellular organelles in the CA1 area of the hippocampus of the two groups of mice using transmission electron microscopy. Immunofluorescence staining is used to detect the deposition of Aβ in the CA1 area of the hippocampus of the two groups of mice. ELISA is used to detect the levels and contents of serum estrogen, ROS, SOD, and MDA, and Western blot is used to determine the expression levels of ERα and ERβ. Result: As the age increased, the escape latency of the ovx group mice in the water maze test gradually prolonged, the deposition of Aβ in the hippocampal CA1 area increased, the mitochondrial swelling of hippocampal neurons increased, and a large amount of lipofuscin and amyloid deposition were observed in the cytoplasm. The serum estradiol level and SOD activity decrease, while the ROS level and MDA content increase. The expression of ERα and ERβ in hippocampal tissue decreases. Conclusion: Ovariectomy in mice with low estrogen status may exacerbate hippocampal Aβ deposition and age-dependent cognitive decline.