2022 Alzheimer's Association Research Fellowship (AARF)
Glial cell-surface proteomics for brain aging and Alzheimer’s Disease
Can impairments in communication between nerve cells and immune cells contribute to the brain changes found in Alzheimer’s?
Madeline Burns, Ph.D.
Baylor College of Medicine
Houston, TX - United States
Background
Alzheimer’s is a progressive brain disorder and is associated with hallmark brain changes including the accumulation of the proteins beta-amyloid and tau into abnormal plaques and tangles, respectively. Studies have suggested that the development of plaques and tangles may impair nerve cell communication in the brain. These communication impairments include both nerve cell-to-nerve cell communication as well as nerve cell-to-glial cell communication.
Glial cells are important in maintaining healthy nerve cells by providing nutrients and immune support. Nerve cell-to-glial cell communication uses specialized proteins on the surface of glial cells. Research has suggested that in Alzheimer’s, impairments in the specialized proteins on the glial cells can contribute nerve cell death and increases in the beta-amyloid and tau. Understanding these specialized proteins is important to further understand the connections between nerve cells and glial cells and how these proteins change throughout normal aging and disease progression.
Research Plan
Dr. Burns and colleagues aim to study how the specialized proteins on the glial cells differ through normal aging and in Alzheimer’s. This may help pinpoint which glial cell surface proteins are dysregulated in Alzheimer’s contributing to the impairments in nerve cell and glial cell communication. To do this, they will use the fruit fly model, which is an important tool in molecular biology for studying multiple proteins and genes rapidly. Dr. Burns research group will investigate surface proteins in the brains of young, old, and genetically engineered Alzheimer’s-like flies using advanced computational methods known as “omics.” They will combine both proteomics, which is the study of the structure and functions of proteins made by cells, and transcriptomics, which is the study of how gene activity is turned “on” or “off” within a cell. This study will help identify changes in proteins and genes during aging and disease. Once they have identified the surface proteins that are dysregulated, they will work to understand what biological mechanisms these surface proteins are involved in.
Impact
If successful, this study will give a better understanding as to why the dysregulation of surface proteins on glial cells may lead to the type of brain damage found in Alzheimer’s. It may also uncover novel glial cell targets. Additionally, findings from this study using fruit flies can be readily translated in mouse and human models.