2022 Alzheimer's Association Research Grant (AARG)

Prenatal Stress as a Risk Factor for Alzheimer's Disease.

How might stress experienced by a pregnant mother impact Alzheimer’s risk in children?

Bianca Ambrogina Silva, Ph.D.
Institute of Neuroscience, CNR
Pisa, Italy

Background

Researchers believe that Alzheimer’s, like other chronic diseases, develops over time as a result of multiple factors, such as lifestyle, environment, and genetics, rather than a single cause. Scientists are studying several life course-related factors, including education, exercise, nutrition, and socioeconomic status, for their impacts on the development and progression of Alzheimer’s. However, most of these studies look at individuals in middle or old age. Little is known about how early life and prenatal environment can impact Alzheimer’s and dementia risk.

Based on initial studies using genetically engineered Alzheimer’s-like mice, Dr. Bianca Ambrogina Silva and colleagues believe that stress experienced by pregnant mothers may activate a pro-inflammatory biological cascade that translates maternal stress into increased vulnerability to Alzheimer’s in their children.

Research Plan

Dr. Silva and colleagues will study the links between prenatal maternal stress, immune activation, and Alzheimer’s risk using genetically engineered Alzheimer’s-like mice. First, the researchers will investigate the impacts of stress in pregnant female mice on immune cells and gene activity in both mother and embryo. Next, the team will study the offspring of stressed mothers at different time points after birth, ranging from before Alzheimer’s symptoms arise to after disease onset in the mice. They will conduct behavioral tests on the mice as well as evaluate biological brain changes associated with Alzheimer’s. Finally, based on the results from these experiments, Dr. Silva and colleagues will design a targeted approach to counteract the identified inflammatory pathways that are activated by the maternal stress. The researchers will administer medications and nutritional compounds with specific anti-inflammatory properties to the mice at different developmental stages to try to prevent Alzheimer’s-like symptoms from emerging.

Impact

The findings may support the importance of maternal well-being during pregnancy as a novel factor in Alzheimer’s prevention. If successful, the results may identify new targets for future Alzheimer’s therapy and prevention.