The Role of APOE Genotpye, Sex, and 17ß-Estradiol in Memory Consolidation in a Mouse Model of Alzheimer's Disease
Mentor 1
Karyn Frick
Location
Union Wisconsin Room
Start Date
5-4-2019 1:30 PM
End Date
5-4-2019 3:30 PM
Description
The APOE4 genotype is the leading genetic risk factor for Alzheimer’s disease (AD), and women APOE4 carriers are more likely than women without APOE4 and men of any APOE genotype to develop AD. APOE4 status, combined with estrogen loss after menopause, places women at greatest risk of developing AD. Our lab and others have previously shown that the potent estrogen 17ß-estradiol (E2) enhances memory in young and aging female mice. However, the interactions among APOE genotype, sex, and estradiol are not well characterized. To address this, two studies were performed. First, to examine effects of sex and APOE genotype on memory, 6 month-old gonadally-intact males and females expressing 5 familial AD mutations (5xFAD-Tg) and human APOE3 (E3FAD) or APOE4 (E4FAD) were trained on object recognition (OR) and object placement (OP). In both tasks, male E3FAD mice exhibited intact memory, whereas E3FAD females and E4FADs of either sex did not, suggesting preserved memory in E3FAD males and impaired memory in E4FAD mice of either sex. To test the extent to which E2 mediates memory consolidation in E3FAD and E4FAD females, ovariectomized female E3FAD and E4FAD mice were trained in the OR and OP tasks. Mice received a post-training infusion of E2 into the dorsal hippocampus and then tested after a 4 or 24-hour delay. In both tasks, E3FAD females receiving E2 had advanced memory but E4FAD females did not. Current studies are characterizing the effects of APOE genotype, sex, and E2 treatment on hippocampal cell signaling and dendritic morphology.
The Role of APOE Genotpye, Sex, and 17ß-Estradiol in Memory Consolidation in a Mouse Model of Alzheimer's Disease
Union Wisconsin Room
The APOE4 genotype is the leading genetic risk factor for Alzheimer’s disease (AD), and women APOE4 carriers are more likely than women without APOE4 and men of any APOE genotype to develop AD. APOE4 status, combined with estrogen loss after menopause, places women at greatest risk of developing AD. Our lab and others have previously shown that the potent estrogen 17ß-estradiol (E2) enhances memory in young and aging female mice. However, the interactions among APOE genotype, sex, and estradiol are not well characterized. To address this, two studies were performed. First, to examine effects of sex and APOE genotype on memory, 6 month-old gonadally-intact males and females expressing 5 familial AD mutations (5xFAD-Tg) and human APOE3 (E3FAD) or APOE4 (E4FAD) were trained on object recognition (OR) and object placement (OP). In both tasks, male E3FAD mice exhibited intact memory, whereas E3FAD females and E4FADs of either sex did not, suggesting preserved memory in E3FAD males and impaired memory in E4FAD mice of either sex. To test the extent to which E2 mediates memory consolidation in E3FAD and E4FAD females, ovariectomized female E3FAD and E4FAD mice were trained in the OR and OP tasks. Mice received a post-training infusion of E2 into the dorsal hippocampus and then tested after a 4 or 24-hour delay. In both tasks, E3FAD females receiving E2 had advanced memory but E4FAD females did not. Current studies are characterizing the effects of APOE genotype, sex, and E2 treatment on hippocampal cell signaling and dendritic morphology.
