Reproductive experience and APOEe4 genotype interact to influence neuroplasticity and neuroinflammation in the middle‐aged brain

Females have a greater lifetime risk of Alzheimer’s disease (AD) compared to males, differences which are further exacerbated with possession of APOEe4 alleles, the greatest genetic risk factor for sporadic AD. Although studying sex and gender differences is important, so is studying sex‐linked factors such as parity (pregnancy and motherhood). Previous parity influences brain aging trajectories in both humans and rodents and may be associated with a greater risk of AD and greater neuropathology. Neuroinflammation is increased with AD, reduces hippocampal neurogenesis, and activates the tryptophan‐kynurenine pathway (TKP), and all these factors are influenced by aging and parity. We investigated whether previous parity influences neuroinflammation and neuroplasticity in middle‐aged rats, dependent on APOEe4 genotype.