Sex-Specific Factors And Apoeε4 Genotype Alter Functional Connectivity At Middle Age
Our brains change as we age, and these changes are influenced by a variety of factors, including our sex and unique life experiences. One significant factor for females is “parity,” which refers to the experience of pregnancy and parenthood. We know that a gene called APOEε4 is a major genetic risk factor for Alzheimer’s disease, and its effects can be different in males and females.
Recent research explored how past pregnancies and the APOEε4 gene interact to affect how brain regions connect and work together in middle age. The study used middle-aged rats, some of whom had the human version of the APOEε4 gene and some who did not, and compared those who had never given birth to those who had one litter.
The findings revealed some important differences. Rats with the APOEε4 gene who had previously given birth showed less activity in several brain areas crucial for memory and reward processing, like the dorsal striatum, nucleus accumbens, frontal cortex, and retrosplenial cortex. Interestingly, rats without the APOEε4 gene who had given birth showed more organized and efficient brain communication networks.
Furthermore, the study found that the way different brain regions influenced each other within these networks changed based on both prior pregnancies and the presence of the APOEε4 gene. The activity of newly formed brain cells in a memory-related area called the hippocampus, combined with other brain regions, could predict how well the rats performed on cognitive tasks, depending on their reproductive history and genetic makeup.
These results highlight that past reproductive experiences have a lasting impact on brain health and how our brains age. They underscore the need to consider these sex-specific factors when studying brain aging and diseases like Alzheimer’s, especially since women are disproportionately affected by the disease.