2023 Alzheimer's Association Research Grant (AARG)
Molecular simulations to investigate protective mutations of APOE proteins
What are the mechanisms by which APOE genetic variants contribute to Alzheimer’s progression?
Qing Shao, Ph.D.
University of Kentucky Research Foundation
Lexington, KY - United States
Background
The apolipoprotein E (APOE) gene provides instructions for making ApoE, a protein believed to help carry lipids (fats) throughout the body. There are several genetic variations of APOE, including APOE-e2, APOE-e3 and APOE-e4. Studies have shown that in some populations, individuals who possess APOE-e4 have an increased risk for developing Alzheimer’s, compared to individuals with other APOE variations. However, the mechanisms linking APOE variations to Alzheimer’s risk and progression of the disease are not fully understood.
Research Plan
Dr. Qing Shao and colleagues will study how the APOE variations change the structure of the ApoE protein and the impact those structural changes have on ApoE’s function in the brain. First, the researchers will use advanced computer modeling techniques to examine the relationship between variations, or changes in the DNA sequence, in APOE and changes in the three-dimensional structure of the ApoE protein. Using the same computer modeling techniques, the team will then study how these mutations impact ApoE’s ability to physically interact with lipids and other proteins in the cell.
Impact
The study results could help us better understand the underlying mechanisms by which APOE variations contribute to one’s risk of developing Alzheimer’s. If successful, the findings could also lead to novel therapies that target the ApoE protein to slow Alzheimer’s progression.