2024 Alzheimer's Association Research Fellowship (AARF)
LACTB as a novel mitochondrial AD risk gene in microglial cells
How does LACTB impact microglial function in Alzheimer’s?
Carmen Romero-Molina, Ph.D.
Icahn School of Medicine at Mount Sinai
New York, NY - United States
Background
Microglia are the primary immune cells of the brain and play a major role helping to maintain healthy nerve cells. Microglia also identify and help remove unwanted proteins from the brain, including beta-amyloid plaques and tau tangles, two hallmark brain changes in Alzheimer’s. While microglia are necessary to keep the brain working properly, increased activity of microglia can lead to brain inflammation, which can damage nearby nerve cells and is common in individuals with Alzheimer’s. Specialized structures inside microglia cells called mitochondria — the powerhouse of energy generation for the cells — have a specific genetic make-up that can influence whether microglia remain healthy or contribute to Alzheimer’s 's-related brain changes. One important gene that can be “turned on” in mitochondria is lactamase B or LACTB. Previous studies suggest that lower levels of LACTB may be protective against Alzheimer’s. This study will investigate how LACTB influences microglial function in Alzheimer’s.
Research Plan
In this study, Dr. Romero-Molina and colleagues will use a specialized type of stem cell collected from adult human tissue called human induced pluripotent stem cells (hiPSCs). These are adult human skin cells that can be “reprogrammed” into any type of cell in the human body and grown in laboratory dishes. Researchers will reprogram them to become microglia with and without the LACTB gene.
Next, researchers will study differences in genetically engineered Alzheimer’s-like mice that have either normal microglia or microglia without LACTB. This will allow the research team to study the impact of LACTB on microglial function in the context of Alzheimer’s-associated brain changes.
Impact
This study may contribute to our understanding of LACTB and the potential of LACTB as a therapeutic target.