2024 Alzheimer's Association Research Fellowship to Promote Diversity (AARF-D)
Role of cholesterol metabolism to microglia reactivity and tau spreading
How do cholesterol levels in the brain contribute to Alzheimer’s brain changes and disease progression?
Matheus Rodrigues, PhD
University of Pittsburgh
Pittsburgh, PA - United States
Background
Nerve cells in the brain use cholesterol as both a source of energy and to maintain their cell structures. Studies have shown that cholesterol and its metabolism (the process by which cholesterol is made and broken down or stored) in nerve cells are vital to healthy brain function and may play a role in the progression of Alzheimer’s and other dementia. However, the precise mechanisms linking cholesterol metabolism and Alzheimer’s are unknown.
In preliminary studies, Dr. Matheus Rodrigues and colleagues have shown that changes in cholesterol metabolism can impact the activity of microglia, the primary immune cells in the brain. Since microglia activity becomes altered during Alzheimer’s progression, these findings suggest a link between cholesterol metabolism, microglia activity, and Alzheimer’s.
Research Plan
For their project, Dr. Rodrigues and the team will measure cholesterol levels in brain tissue from individuals who had Alzheimer’s. They will next associate the extent of cholesterol levels within each tissue sample with changes in proteins involved in cholesterol metabolism and the hallmark brain changes that are seen in Alzheimer’s, including the accumulation of amyloid plaques and tau tangles. The researchers will then measure levels of microglia activity in the same brain tissue to examine how changes in cholesterol-related proteins impact microglia activity.
Lastly, once they have identified the cholesterol-related proteins that are associated with both microglia activity and the hallmark brain changes in Alzheimer’s, the team will measure the levels of those proteins in the cerebral spinal fluid (the fluid that surrounds the spinal cord) from individuals with Alzheimer’s.
Impact
This study will provide a deeper understanding of how changes in cholesterol metabolism may contribute to Alzheimer’s progression. The findings may support future investigation into the use of cholesterol-lowering therapies as a potential therapeutic approach for Alzheimer’s.