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2014 Grants - Bradshaw
Genetics, Function and Small Molecules: Targeting the CD33 Alzheimer’s Locus
Elizabeth Bradshaw, Ph.D.
Brigham and Women’s Hospital
2014 Investigator-Initiated Research Grant: Discovery-Validation of Therapeutic Targets for Developing Novel Interventions for Alzheimer’s Disease
Recent evidence suggests that the immune system plays an important role in Alzheimer’s disease and scientists have identified several immune-related genetic characteristics that may be associated with increased risk of developing Alzheimer’s. For instance, studies have found that different variations of the CD33 gene, which code for the CD33 protein found on the surface of immune cells, may impact Alzheimer’s disease risk.
Elizabeth Bradshaw, Ph.D., and colleagues have found that certain genetic variations of the CD33 gene lead to increased levels of the CD33 protein on the surface of immune cells circulating in the body and entering the brain. In addition, people who have one of these CD33 genetic variations have higher levels of amyloid plaques in the brain, a hallmark feature of Alzheimer’s disease.
For the current studies, Dr. Bradshaw’s team has proposed a series of experiments to further characterize how genetic variations in CD33 affect the risk of developing Alzheimer’s disease and the accumulation of amyloid plaques in the brain. They have also identified two possible drug candidates that can reduce CD33, and will study how these drugs affect CD33 levels on the surface of immune cells isolated from people with and without evidence of amyloid deposits in their brain. These studies could lead to the identification of new drug candidates that may be able to be tested for their ability to slow or halt the progression of Alzheimer’s disease.