2024 Alzheimer's Association Research Grant to Promote Diversity (AARG-D)
Targeting mitochondrial metabolism in AD
How does the brain’s metabolism change in Alzheimer’s?
Xuewei Zhu, Ph.D.
Wake Forest University Health Sciences
Winston-Salem, NC - United States
Background
Metabolism is the process of breaking down foods into energy in the body. During this process, the body produces different compounds called metabolites that are transported throughout the body to cells so that cells can carry out vital functions. For example, metabolism allows brain cells to grow and supports healthy brain function. However, it’s unclear how brain metabolism changes in Alzheimer’s.
Research Plan
For their studies, Dr. Xuewei Zhu and team will first study how a specific metabolic protein called pyruvate dehydrogenase kinase (PDHK) may lead to the brain metabolism changes observed in Alzheimer’s. To do this, the researchers will treat genetically engineered Alzheimer’s-like mice with a small molecule that inhibits PDHK activity, and measure changes in levels of metabolites in the brains of these mice. Lastly, the team will examine whether inhibiting PDHK improves overall brain health in genetically engineered Alzheimer’s-like mice.
Impact
The results of this project may help us better understand how changes in brain metabolism impact Alzheimer’s. If successful, the findings could help identify new therapeutic avenues that could target brain metabolism as a treatment for Alzheimer’s.