Mostly Alzheimer’s disease (AD) cases are sporadic, with no clear intrinsic triggering mechanisms but with identified risk factors. Environmental stress factors are thought to account for approximately 25–40% of the risk to develop AD. Elevated levels of glucocorticoids and irregulated hypothalamic-pituitary-adrenal (HPA) axis (or stress axis) are consistently observed in patients of AD. In rodent experimental models of AD, a dysregulation of HPA axis is also observed, and either stress or direct treatment with glucocorticoids in these models worsens hallmarks of AD at the molecular, histological, and behavioral levels.