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 260
Start Date
27-4-2018 12:20 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 who carry other APOE genotypes 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 issue, two studies were performed. First, to examine effects of sex and APOE genotype on memory, 6 month-old gonadally-intact male and female expressing 5 familial AD mutations (5xFAD-Tg) and human APOE3 (E3FAD) or APOE4 (E4FAD) were trained on object recognition (OR) and object placement (OP) tasks to test object recognition and spatial memory formation. In both tasks, male E3FAD mice exhibited intact memory, whereas E3FAD females and E4FADs of either sex did not, suggesting preserved memory function in E3FAD males relative to females, 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 as above. Mice received a post-training infusion of E2 into the dorsal hippocampus and then memory was tested after a 4 or 24 hour delay. Preliminary data indicate that E2 may enhance object recognition memory in E3FAD females but not E4FAD females. Future studies will characterize 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 260
The APOE4 genotype is the leading genetic risk factor for Alzheimer’s disease (AD), and women APOE4 carriers are more likely than women who carry other APOE genotypes 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 issue, two studies were performed. First, to examine effects of sex and APOE genotype on memory, 6 month-old gonadally-intact male and female expressing 5 familial AD mutations (5xFAD-Tg) and human APOE3 (E3FAD) or APOE4 (E4FAD) were trained on object recognition (OR) and object placement (OP) tasks to test object recognition and spatial memory formation. In both tasks, male E3FAD mice exhibited intact memory, whereas E3FAD females and E4FADs of either sex did not, suggesting preserved memory function in E3FAD males relative to females, 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 as above. Mice received a post-training infusion of E2 into the dorsal hippocampus and then memory was tested after a 4 or 24 hour delay. Preliminary data indicate that E2 may enhance object recognition memory in E3FAD females but not E4FAD females. Future studies will characterize the effects of APOE genotype, sex, and E2 treatment on hippocampal cell signaling and dendritic morphology.
