Objective The present study aimed 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 receiving an ovariectomy at different ages. Methods 3-month-old APP/PS1 female mice were divided into three groups, with 20 mice in each group. Ten mice were treated with bilateral ovarian resection via abdominal surgery as the model (ovx)group. The 10 mice in the control (sham) group underwent surgery in which an equivalent volume fat was removed from the corresponding area. After 3, 4, and 5 months, APP/PS1 mice were assigned to 6-, 7-, and 8-month age groups. The cognitive function of the APP/PS1 mice of different ages was evaluated using the Morris water maze. Morphological changes to intracellular organelles in the CA1 area of the hippocampus of the two groups of mice were observed using transmission electron microscopy. Immunofluorescence staining was used to detect the deposition of Aβ in the CA1 area of the hippocampus of the two groups of mice. ELISA was used to detect the levels and contents of serum estrogen, ROS, SOD, and MDA, and Western blot was used to determine the expression levels of ERα and ERβ. Results As the ovx group mice increased in age, their escape latency in the water maze test gradually lengthened, the deposition of Aβ in the hippocampal CA1 area increased, the mitochondrial swelling of hippocampal neurons increased, and larger amounts of lipofuscin and amyloid deposition were observed in the cytoplasm. Their serum E2 levels and SOD activity decreased, while their ROS levels and MDA contents increased, and the expression of ERα and ERβ in the hippocampal tissue decreased. Conclusions Ovariectomy in mice with low estrogen status may exacerbate hippocampal Aβ deposition and age-dependent cognitive decline.