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2017 Grants - De Leonibus
Neurobiology of Sex Differences in Memory Capacity in Ageing and Alzheimer’s Disease
Elvira De Leonibus, Ph.D.
2017 Sex and Gender in Alzheimer’s (SAGA) Grant
What are the biological factors that may underlie sex differences in memory loss in Alzheimer’s disease?
Because Alzheimer’s disease is a progressive disorder, researchers are working to characterize the disease at its earliest stages, when treatments may be most effective. Part of this effort involves analyzing subtle changes in brain function, especially memory, which may indicate the risk of developing dementia. One such change is the loss of “memory capacity” or the number of items that one can remember over varying periods of time. Memory capacity begins to decline as early as one’s forties, gradually hindering the ability to reason and solve problems. In initial studies with mice, Elvira De Leonibus, Ph.D., and colleagues found that aging female mice lose memory capacity in different ways from aging male mice. Females preserve their “working” (or short-term) memory capacity better than males, but they show greater declines in long-term memory capacity. These discrepancies suggest that males and females may experience early, age-related brain damage in different brain regions which may impact their risk of developing Alzheimer’s disease.
For their current research grant, Dr. De Leonibus and colleagues will conduct a larger study to explore how declines in memory capacity may differ in male and female mice. Their effort will involve assessments of normally aging mice and of mice genetically engineered to develop Alzheimer’s-like brain changes. The researchers will work to identify the biological mechanisms that may underlie sex-specific loss of memory capacity, including damage to certain brain regions and brain cell communication pathways. They will also examine how the loss of sex hormones in mid-life (especially the loss of estrogen in females) may be involved in these processes.
The results of this project could refine our understanding of how early cognitive decline differs between women and men; and whether these differences may place women at a greater risk for dementia. They could also lead to more refined, sex-specific diagnostic tools for Alzheimer’s disease.