Enhanced activity of hippocampal BACE1 in a mouse model of postmenopausal memory deficits.

Ovarian hormone decline after menopause may influence cognitive performance and increase the risk for Alzheimer's disease (AD) in women. We have recently demonstrated that a combination of ovariectomy and chronic stress (OVX/stress) causes hippocampus-associated cognitive dysfunction in mice. In this study, we examined whether OVX/stress could affect the levels of AD-related molecules in the mouse hippocampus. Female ICR mice were ovariectomized or sham-operated, and then randomly divided into a daily restraint stress (21 days, 6 h/day) or non-stress group. Although OVX or stress alone did not affect beta-site amyloid precursor protein (APP)-cleaving enzyme-1 (BACE1) activity, OVX/stress increased activity in hippocampal CA1 and CA3 regions, compared with other groups. In contrast, OVX/stress did not affect gamma-secretase activity, Abeta(1-40), and phosphorylated-tau levels in the hippocampus. These findings suggest that a stressful life after menopause can influence the levels of AD-related molecules and that BACE1 is the most sensitive molecule for such a situation.