To view an abstract, select an author from the vertical list on the left.
2016 Grants - Belaidi
Iron and Apolipoprotein E Link in the Pathogenesis of Alzheimer’s Disease
Abdel Ali Belaidi, Ph.D.
Florey Institute of Neuroscience and Mental Health
2016 Alzheimer’s Association Research Fellowship to Promote Diversity (AARF-D)
How do variations in the APOE gene affect iron levels in the brain and the risk for Alzheimer’s disease?
People who have certain versions of the apolipoprotein (APOE) gene are known to be at increased risk for Alzheimer’s disease. The APOE-e4 variation is one of the strongest genetic risk factors for the disease, while the APOE-e2 version appears to reduce risk. The underlying mechanisms by which different versions of the APOE gene affect the risk of Alzheimer’s are not well understood. Abdel Ali Belaidi, Ph.D., and colleagues recently found that people APOE-e4 also have increased levels of iron in the brain. Other studies have shown that iron levels are increased in brain tissue from people who had Alzheimer’s disease. It is not yet clear how differences in APOE may influence brain levels of iron and the risk for Alzheimer’s disease.
Dr. Belaidi and colleagues will study the relationship between APOE, iron levels in the brain, and nerve cell function. In previous experiments using nerve cells grown in laboratory dishes, the researchers found that APOE-e4 increased levels of iron in the cells. For their current studies, they will measure the transport of iron into and out of nerve cells that have different versions of the APOE gene (e2, e3, e4). Dr. Belaidi and colleagues will also measure levels of iron in the brains of Alzheimer’s-like mice that have been genetically engineered to carry different versions of the APOE gene. The researchers will study the mice as they age to determine how APOE affects accumulation of iron in the brain across time, and whether this relates to nerve cell death and cognitive decline.
These studies will begin to link together the molecular mechanisms that underlie genetic risk factors, brain levels of iron and Alzheimer’s disease. The results of this work could inform the development of new therapies to regulate brain levels of iron in high-risk individuals to help prevent or slow the progression of Alzheimer’s disease.