2023 Alzheimer's Association Research Grant (AARG)
Novel Immune Cell Bioindicators as Diagnostic and Therapeutic Targets
Which cells might underlie brain inflammation that can occur in Alzheimer’s?
Daniel Hawiger M.D., Ph.D.
Saint Louis University
St. Louis, MO - United States
Background
The body’s immune system is its primary defense against brain changes that occur during Alzheimer’s. Immune cells in the brain help remove unwanted proteins such as beta-amyloid and tau that can accumulate in the brain and are hallmarks of Alzheimer’s. However, studies show that too much immune cell activity in the brain can lead to brain inflammation (neuroinflammation) and damage to brain cells. Researchers are looking for ways to reduce the brain’s immune response to Alzheimer’s without losing its beneficial effects. It can be difficult for researchers to distinguish immune cells in the brain that might lead to damage, from beneficial immune cells.
Research Plan
Dr. Daniel Hawiger and colleagues will study genetic data from immune cell populations associated with different stages in Alzheimer’s progression. Their goal is to uncover biological markers, or biomarkers, that might improve disease diagnostics and treatment over the course of the disease.
To do this, the researchers will study immune cells, including those collected from genetically engineered Alzheimer’s-like mice and from blood samples collected from individuals with Alzheimer’s. The researchers will measure gene activity in the cells and immune-related biomarkers collected from the blood. They will create genetic “signatures” associated with immune cells and determine whether these signatures might be used to help identify different stages of Alzheimer’s.
Next, Dr. Hawiger’s team will change populations of specific immune cells in the brains of the mice. The researchers will do this by treating the mice with different portions of tau protein to trigger different immune responses in the brain. They will test whether changing the immune responses in this way might reverse or slow the disease process.
Impact
This study could uncover new genetic biomarkers for Alzheimer’s. The study will also investigate the therapeutic ability of changing immune cell populations in the brain during Alzheimer’s. Results could lead to the development of immune therapies for Alzheimer’s, including those that are designed to limit damage in the brain caused by neuroinflammation.