2021 Alzheimer's Association Research Grant (AARG)

The Role of Apolipoprotein E4 in Intracellular Lipid Distribution

How does a genetic risk factor for Alzheimer’s in some populations impact the way brain cells store fat?

Lisa Munter, Ph.D.
The Royal Institution for the Advancement of Learning/McGill University
Montreal, Canada

Background

The apolipoprotein E (APOE) gene provides instructions for making the ApoE protein that is thought to help carry fat throughout the body. A variation in the APOE gene, called APOE-e4, is thought in some populations to impact a person’s risk of developing Alzheimer’s. However, the biological mechanism by which APOE-e4 affects the risk of developing Alzheimer’s is still unclear. 

Dr. Lisa Munter and her team recently showed that in brain cells possessing the APOE-e4 variation, fat storage is dysregulated. However, the underlying biological pathways linking APOE-e4, fat storage, and the risk of Alzheimer’s are not known.
 

Research Plan

To investigate the potential roles of APOE-e4 in fat distribution within cells, Dr. Munter and colleagues will study mouse brain cells grown in laboratory dishes and genetically engineered Alzheimer’s-like mice.

The researchers will screen FDA-approved drugs for their impact on fat storage in brain cells to see if any may be able to be repurposed to counteract the effects of APOE-e4 on fat storage biology. Dr. Munter and research team will also study the underlying biological mechanisms of fat accumulation and distribution within brain cells. In addition, the researchers will study if APOE-e4 interacts with other fat transporters and how these interactions may impact fat storage dysregulation.
 

Impact

The results of this project may help increase understanding of the biological underpinnings associated with Alzheimer’s as well as identify whether existing approved drugs may impact this biology. If successful, the findings may also be relevant for other neurodegenerative diseases that involve fat storage dysregulation, such as Huntington’s disease and vascular dementia.