2023 Sex and Gender in Alzheimer’s (SAGA) Grant (SAGA)
How does pregnancy with Down syndrome causes maternal Alzheimer disease?
How does pregnancy with a Down syndrome baby lead to an increased risk of Alzheimer’s to the mother?
Eitan Okun, Ph.D.
Bar-Ilan University
Ramat-Gan, Israel
Background
The Alzheimer’s rates for mothers who were pregnant at a young age (35 years or younger) with a child who had Down syndrome is higher than the rate for women in general and mothers who had children with non-Down syndrome intellectual disabilities. Individuals who have Down syndrome also have a high risk of developing Alzheimer's, and the disease often begins to develop when they are still in their 30s and 40s. It is not known how pregnancy with a individual with Down syndrome could confer increased risk of Alzheimer’s to mothers.
In initial research, Dr. Okun studied amyloid precursor protein (APP) fragments, which can accumulate in the brain as beta-amyloid plaques, a hallmark brain change in Alzheimer’s. They found that mice, following pregnancy with genetically-engineered Alzheimer’s-like mice, had fragments of APP in their brains. They hypothesize that there can be maternal-fetal transfer of APP fragments during pregnancy that can enter into the mothers brain.
Research Plan
Dr. Okun will mate healthy female mice with genetically engineered Alzheimer’s-like male mice to determine how APP fragments transfer from fetus to mother—whether by DNA, mRNA or protein, and if the molecules travel via extracellular vesicles (bubble-like structures that are released by cells and carry molecules to other parts of the body).
They will also assess whether the transfer of APP fragments from fetus to mother leads to cognitive decline in the mother as she ages using well established cognitive tests for mice. Finally, they will use a genetic engineering technique to remove fetal cells from the mother to see if this prevents any observed cognitive decline.
Impact
The results of this study may help understand how a fetus could confer Alzheimer’s risk to the mother, which may pave the way for future therapies to prevent or block it.