Grant: Travel Awards - Institute Community Support

Females have a higher lifetime risk and show greater symptoms of Alzheimer's disease (AD) than males. The strongest genetic risk factor for AD is having APOEe4 alleles, and interestingly, females with APOEe4 alleles show greater risk and burden of AD than their male counterparts. To better understand how AD affects females, it is necessary to investigate the influence of female-specific factors, like reproductive experience. Indeed, reproductive experience shapes the aging brain and has been associated with greater risk and earlier age of onset of AD. The objective of the present research is to examine the long-term effects of reproductive experience on markers of brain health and how APOEe4 genotype may alter these relationships. We used a sporadic AD rat model that expresses the human form of APOEe4. Wildtype and APOEe4 rats either had no reproductive experience or one reproductive experience. Brains were extracted at middle age (13-14 months old) to examine plasticity and inflammation in the brain, which are both markers of brain health. We found that wildtype rats with one reproductive experience showed greater plasticity in the brain, quantified as greater number of new-born neurons, compared to rats with no reproductive experience, which is consistent with previous research. Interestingly, APOEe4 rats with one reproductive experience showed the opposite, as they had fewer new-born neurons compared to wildtype rats. APOEe4 rats with one reproductive experience also had a unique inflammatory profile in the brain compared to other groups. Together, these findings demonstrate that reproductive experience alters plasticity and inflammation in the brain depending on APOEe4 genotype, and underscores the importance of considering female-specific factors in aging and AD research.