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Depressive-like and anxiety-like symptoms in 16-week-old APP/PS1 mice.APP/PS1 mice showed low levels of serum corticosterone.Chronic mild stress aggravated anxiety-like behaviors, but not depressive-like behaviors of APP/PS1 mice.CMS caused more severe neuroinflammation of APP/PS1 mice.Early Alzheimer’s disease (AD) and depression share many symptoms, but the underlying mechanisms are not clear. Therefore, characterizing the shared and different biological changes between the two disorders will be helpful in making an early diagnosis and planning treatment. In the present study, 8-week-old APPSwe/PS1dE9 transgenic mice received chronic mild stress (CMS) for 8 weeks followed by a series of behavioral, biochemical and pathological analyses. APPSwe/PS1dE9 mice showed depressive- and anxiety-like behaviors, and reduced sociability, accompanied by high levels of soluble beta-amyloid, glial activation, neuroinflammation and brain derived neurotrophic factor signaling disturbance in the hippocampus. Notably, APPSwe/PS1dE9 mice exposure to CMS partially aggravated anxiety-like states rather than depressive-like responses and sociability deficits, with further elevated hippocampal interleukin-6 and tumor necrosis factor-α levels. These results demonstrated that young adult APPSwe/PS1dE9 have depressive- and anxiety-like phenotypes that were resistant to CMS compared to wild-type mice. This finding may help to understand the pathogenic mechanism of psychiatric symptoms associated with early AD.