2023 Alzheimer's Association Clinician Scientist Fellowship (AACSF)
Genomic integrity in Alzheimer's disease
How do immune cells influence nerve cell damage in Alzheimer’s?
Johannes Schlachetzki, M.D.
University of California
La Jolla, CA - United States
Background
Identifying the genetic risk factors that may increase an individual's risk for developing Alzheimer’s is a major research focus in the field. Studies have shown that accumulation of damage to an individual’s DNA (genetic code) in brain nerve cells may increase one’s risk of developing Alzheimer’s. However, the mechanisms are unknown.
Microglia are the primary immune cells in the brain that serve as one of the first defenses against nerve cell damage. Increased and long-term activation of the microglia can lead to brain inflammation which can lead to damage to nearby nerve cells. Dr. Johannes Schlachetzki hypothesized that microglia may contribute to the DNA damage seen in nerve cells in Alzheimer’s.
Research Plan
Dr. Schlachetzki and colleagues will measure the levels of DNA damage in nerve cells from brain tissue from individuals who had Alzheimer’s and cognitively unimpaired individuals to examine differences in nerve cell DNA damage linked to Alzheimer’s. Next, the team will create nerve cells and microglia using a specialized type of stem cell called iPSCs (induced Pluripotent Stem Cells) which can be programmed into any type of cell in the body. They will then expose the nerve cells to small molecules released by the microglia cells to examine whether microglia impact DNA damage in nerve cells.
Impact
The results of this study could shed new light on how microglia impact the nerve cell DNA damage seen in Alzheimer’s. If successful, the findings could inform the development of novel strategies targeting microglia for treatment of Alzheimer’s.