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2014 Grants - Gilbert
Identification of Mutations and Transcription in LOAD GWAS Regions
John Ray Gilbert, Ph.D.
University of Miami
2014 Investigator-Initiated Research Grant: Biological Underpinnings of Genetic Risk Factors in Alzheimer’s Disease
Scientists have known for several years that one of the strongest risk factors for late-onset Alzheimer’s disease (LOAD) is the epsilon-4 variant of the apolipoprotein E gene (APOE-ɛ4). However, this genetic variation accounts for only a fraction of LOAD cases (i.e. not everyone inherits the APO-ɛ4 gene). An important goal of current research is to identify additional genetic risk factors that could contribute to the development of Alzheimer’s disease.
More recently, scientists have been using a method known as genome-wide association studies (GWAS) to identify regions of DNA (genetic material that provides instruction for making proteins) in which certain changes are associated with increased risk of late-onset Alzheimer’s disease. Using this method, researchers have identified at least 20 such DNA regions. However, these 20 regions may contain the genetic codes for making as many as 80 different proteins. At this time, it is not known which of these proteins and which genetic variations are responsible for an increased risk of Alzheimer’s disease.
John Ray Gilbert, Ph.D., and colleagues have proposed an in-depth study of the 20 regions of DNA and the proteins for which they are responsible for making. Using brain tissue from people who had late-onset Alzheimer’s disease, the researchers will study the proteins coded by these regions of DNA and how brain levels of these proteins are altered in people with different genetic variations. These studies may help to identify which genetic variations and proteins are linked with the increased risk of late-onset Alzheimer’s disease. Identifying novel genetic risk factors will provide information on the mechanisms of disease development and may help scientists devise drugs or lifestyle changes to target these mechanisms to lower a person’s risk.