2023 Alzheimer's Association Research Grant to Promote Diversity (AARG-D)
Interactions of sex hormone receptors and stress in AD
What role do sex hormones play in the progression of Alzheimer’s?
Damian Zuloaga, Ph.D.
Research Foundation of SUNY - University at Albany
Albany, NY - United States
Background
Research has shown a strong link between stress and Alzheimer’s, with individuals suffering from severe stress being twice as likely to develop Alzheimer’s. It has also been observed that the loss of sex hormones, hormones critical in the development and maintenance of sexual features, is also linked to higher risk of Alzheimer’s. There is a link between key sex hormones and hormones related to stress, collectively known as the HPA axis. Of particular interest are the sex hormones androgen and estrogen which help control the levels of glucocorticoids (stress hormones) and limit the impact stress can have on the body. Increased levels of glucocorticoids have been linked to a higher risk of Alzheimer’s. By modifying levels of these sex hormones, there is a potential for limiting the contributions of glucocorticoids to Alzheimer’s pathology.
Research Plan
Zuloaga and colleagues will investigate how the HPA axis and sex hormones interact and contribute to Alzheimer’s. In particular, they will focus on the activation of the estrogen receptor and the androgen receptor, two proteins on the surface of cells critical for the cells to use estrogen and androgen.
They will do this by studying the effects of reducing the levels of the sex hormones in a genetically engineered Alzheimer’s-like mouse model which develop beta-amyloid plaques, a hallmark brain change in Alzheimer’s and cognitive impairments. Using this model, they can measure the build up of glucocorticoids and the increase of beta-amyloid plaques . They will use different drugs to activate the receptors for the sex hormones and study the changes in levels of beta-amyloid plaques. They will be measuring levels of glucocorticoids and testing the cognitive abilities of the mice as well with different treatments.
Impact
This project will help to clarify the connection between stress hormones, sex hormones, and Alzheimer’s. Additionally, this study will test whether or not activation of sex hormone receptors later in life can help to delay the onset of Alzheimer’s.