Objective:To examine the effects of estrogen deficiency on cognitive impairment and cerebral pathological changes in APP/PS1 double transgenic mice

as well as on the expression of estrogen receptor β（ERβ）and glycogen synthase kinase-3β（GSK-3β）

so as to clarify the molecular mechanisms of estrogen deficiency leading to Alzheimer’s disease（AD）. Methods:The 3-month-old APP/PS1 double transgenic mice were randomly divided into sham-operated group（AD-Sham）（n=10）and ovariectomized group（n=10）

and age-matched wild type mice were as controls（WT）（n=10）. Mice were examined at 1 month and 5 months after OVX or sham operation. The Morris water maze test

radioimmunoassay

Western blot and immunofluorescent staining were used to detect the learning and memory ability and the serum estrogen levels of mice

and senile plaques

ERβ and GSK-3βprotein levels in the brain of mice. Results:Radioimmunoassay showed that the serum estradiol levels was dropped significantly at 1 month（F=22.441

P=0.002）and 5 months（F=210.959

P=0.000）after OVX

and the uterine began to atrophy at 1 month after OVX

and the sizes of uterine further atrophy at 5 months after OVX. Morris water maze test showed that compared with those of AD-Sham group

the escape latency and the path length were increased significantly and the passing times were decreased significantly of AD-OVX group at 1 month after OVX（P<0.05）. With the time following after OVX

the escape latency

the path length and the passing times were showed a further decline（P<0.05）. If results showed that compared with that of the AD-Sham group

the number of senile plaques was begun to increase in the cortex in the AD-OVX group at 1 month after OVX（5.667±0.577 vs. 3.333±0.577

P=0.023）as the incidence of OVX

the number of senile plaques was increased significantly in the hippocampus（6.333±1.528 vs. 3.667±0.577

P=0.013）and cortex（11.667±1.528 vs. 6.000±1.000

P=0.001）.Western blot showed that compared with that of WT group

the ERβ was abnormally expressed in AD-Sham group（P<0.05）. The expression of ERβ was down regulated at 1 month（F=65.625

P=0.000）and 5 months（F=18.462

P=0.003）after OVX（P<0.05）

while a similarly consistent trend was found in the expression of p-GSK-3β（ser9）（P<0.05）

although the expression of total GSK-3βshowed no differences. Conclusion:Estrogen deficiency induces cognitive dysfunction and aggravates pathological in APP/PS1 mice

the mechanism is related to the signaling pathway of ERβ/GSK-3β.