Grant: Travel Awards - Institute Community Support

Women are more likely to be diagnosed with Alzheimer's Disease (AD) and show greater AD neuropathology and cognitive decline compared to men. Pregnancy and motherhood (parity) play important roles in the aging brain; increased parity is associated with a greater risk of dementia, AD, neuropathology, and an earlier age of AD onset. Research in our laboratory has shown that parity influences hippocampal neuroplasticity and cognition in middle-age rats. APOE4, a major genetic risk factor for AD, has been shown to interact with parity to influence AD pathology, age of AD onset, and cognition. The objective of this project is to determine how previous parity interacts with APOE genotype to influence cognitive decline in older female rats. We used a rat model of AD that expresses the human form of APOE4. Age-matched APOE4 and wild-type female rats were either nulliparous (never mothered and with no sexual experience) or primiparous (first time mothers). The primiparous (WT and APOE4) female rats were bred at 5 months old in our animal facility. Pups were culled and the sex ratio of the litters were recorded. Maternal observations were completed twice a day, on days 2 to 6 postpartum. All rats were aged and then trained and tested during middle-age (9 months postpartum; equivalent to 13-14 months old) on the delayed win-shift Radial Arm Maze (RAM), a spatial working memory task mediated by the prefrontal cortex and hippocampus. I am currently analyzing the data for this study. It is hypothesized that APOE4 primiparous rats will perform worse than APOE4 nulliparous rats, and APOE4 rats will perform worse than wild-type rats, in the RAM. It is further hypothesized that APOE4 genotype interacts with parity to contribute to cognitive decline.These results will offer insight into how parity and genotype are linked to cognition. This has implications for the importance of tailored treatments based on the genotype and reproductive history of women with AD.