“Brain aging is also about brain development, and understanding sex differences in brain development is essential to understanding sex differences in the aging brain,” said corresponding author Jill M. Goldstein, PhD. , MPH, founder and executive director of the Center for Sex Innovation. Differences in Medicine from Massachusetts General Hospital, founding member of the Mass General Brigham Health System and professor of psychiatry and medicine at Harvard Medical School. “This paper is a first step toward studying the fetal origins of Alzheimer’s disease, which, like many chronic diseases, develops throughout life and is influenced by early development in ways that we could not normally consider.”

This study was based on results from a cohort established more than 60 years ago, which includes the adult offspring of nearly 18,000 pregnancies between 1959 and 1966, followed as part of the New England Family Study (NEFS). The present investigation included 204 individuals born during the study who may or may not have been exposed to an adverse event. in utero immune environment (i.e., high levels of immune markers, such as the cytokines IL-6 and TNF-a) and followed up to midlife 50 years later. The team used functional brain imaging to examine the impact of this early exposure on brain regions of memory circuits that are dense with cytokine receptors and sex hormone receptors and show sex differences in development and functioning from fetal development.

Researchers found that high levels of IL-6 and TNF-a in mothers during pregnancy were linked to sex differences in unwanted brain activity in memory circuits in offspring later in life. life, especially in postmenopausal women. These women also expressed higher markers of a pro-inflammatory state at midlife. Additionally, researchers saw the impact of these immune markers even earlier, on children’s cognitive performance at age seven, highlighting the link between exposures during pregnancy and brain health later in life. . Their results suggest that elevated maternal prenatal immune activity may contribute to the development of increased immune and stress sensitivity in offspring, which the researchers hypothesize may predispose them to memory disorders, such as MA, later in life, in a sex-dependent manner.

As participants age, researchers continue to follow them to examine amyloid levels and other measures of AD-related pathology to further explore the association between prenatal immunity and AD. Ongoing goals include understanding the mechanisms by which maternal immune activity influences fetal brain development, identifying biomarkers of future memory dysfunction in early midlife, and understanding how other periods development, such as puberty, influence brain aging.

“Although prenatal immune activity can affect offspring brain development, this does not mean that pregnancy is deterministic,” Goldstein said. “Of course, subsequent environmental exposures are essential, as are in utero the environment is important. Fortunately, the brain is exceptionally adaptable, and we want to understand the cognitive, behavioral, and sex-dependent factors associated with risk and resilience in order to intervene early and maintain intact memory function as we age.