Alzheimer’s disease (AD) is a neurodegenerative disorder that is expected to increase in the next years affecting more women than men. Although AD has often been associated with brain ageing it is known for developing across the lifespan. However, the effect of foetal antecedents on brain health later in life, and the role sex differences play in this process are still unclear. In a recent study published in the journal of Molecular Psychiatry (Springer Nature), a team of researchers led by Dr Jill M. Goldstein from Harvard Medical School (Boston, US) investigated the foetal origins of memory performance and the effect of sex differences.
This research involved a cohort of a total of 17,741 pregnancies that were followed between 1959 and 1966 as part of the New England Family Study (NEFS). Maternal prenatal immune abnormalities (i.e. elevated levels of proteins that control inflammatory processes, such as IL-6 and TNF-α) were assessed in blood collected from the women during the beginning of the third trimester of pregnancy, as this is one of the key periods of the sexual differentiation of the human brain. The prenatal cohort included 204 individuals exposed or unexposed to elevated levels of IL-6 and TNF-α and followed into early midlife (i.e. 50 years later), including detailed assessments at the age of 7. The researchers then measured the impact that early exposure to these inflammatory markers has on the offspring’s brain regions associated with associative and verbal memory using brain imaging techniques.
The team found that dysregulated utero maternal immune environment (i.e. elevated levels of IL-6 and TNF-α during pregnancy) impacts memory performance, memory circuitry function, and immune responses in midlife for men and after menopause for women. Moreover, researchers found that the consequences of being exposed to these pro-inflammatory molecules can be seen even earlier, by the age of 7, impacting the cognitive performance of the offspring. Although this study has some limitations (e.g. executive memory should be considered in future studies to fully investigate the impact of maternal prenatal immune abnormalities on the risk for AD), the results of this study suggest that a dysregulation of the maternal immune system function impacts memory performance and memory circuitry in the offspring in the long-term and with sex-dependent effects.