Depressive- and anxiety-like phenotypes in young adult APP(Swe)/PS1(dE9) transgenic mice with insensitivity to chronic mild stress

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 APP(Swe)/PS1(dE9) transgenic mice received chronic mild stress (CMS) for 8 weeks followed by a series of behavioral, biochemical and pathological analyses. APP(Swe)/PS1(dE9) 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, APP(Swe)/PS1(dE9) 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-alpha levels. These results demonstrated that young adult APP(Swe)/PS1(dE9) 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.