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2014 Grants - Mastroeni
Profiling the Gliome in Alzheimer’s Disease
Diego F. Mastroeni, Ph.D.
Banner Sun Health Research Institute
Sun City, Arizona
2014 New Investigator Research Grant
Glial cells, which include astrocytes and microglia, are the “helper” cells of the brain and perform many important functions. They help sustain the health and function of nerve cells, often by providing nutrients and energy and helping to regulate the brain’s immune system. In Alzheimer’s disease, however, glial cell function can become altered and may lead to excess brain inflammation and nerve cell damage and death. It is not known exactly how glial cells become dysfunctional in Alzheimer’s disease, but recent studies suggest that changes in the genes of glial cells may play a role.
Diego F. Mastroeni, Ph.D., and colleagues have been examining the “gliome” (or the complete set of genes found in glial cells) in brain samples from individuals with and without Alzheimer’s disease. Their results showed major genetic differences between the glial cells found in the brains of individuals with Alzheimer’s compared to those who were cognitively normal. Moreover, the genetic changes in the glial cells varied significantly depending on which region of the brain they were located in.
For their current study, Dr. Mastroeni and colleagues will profile genetic changes in astrocytes and microglia within the hippocampus, a brain region important for memory and which is affected early in Alzheimer’s disease. They will also examine the brains of individuals with Parkinson’s disease to examine genetic changes in glial cells within the substantia nigra, a brain region affected in Parkinson’s. They will use sophisticated, laser-based technology to specifically identify and capture glial cells in these regions, and then look for differences in genes involved with inflammation, energy formation, and the ability to eliminate harmful substances. They hypothesize that glial cells in Alzheimer’s and Parkinson’s brains will express higher levels of inflammatory proteins — and lower levels of other proteins — than will glial cells from healthy brains. Such results could shed new light on the genetic basis of glial dysfunction in dementia. It could also lead to more targeted therapies for Alzheimer’s and Parkinson’s diseases.