To view an abstract, select an author from the vertical list on the left.
2013 Grants - Desplats
DNA Methylation Alterations in the Course of Alzheimer's Disease
Paula Alejandra Desplats, Ph.D.
University of California, San Diego
San Diego, California
2013 New Investigator Research Grant to Promote Diversity
Current research suggests that Alzheimer's disease is strongly inheritable. Yet scientists have found limited evidence of the genes involved in Alzheimer's. During recent years, some investigators have observed that a natural process for modifying one's DNA (genetic material) may become altered in people at risk of dementia. This process is called DNA methylation, or the addition of methyl compounds to DNA. Methylation is used to turn genes "on" or "off" during different phases of the body's development, and it helps regulate proper gene expression (the conversion of genes into proteins). But the process may become altered in Alzheimer's and other dementias. Because DNA methylation can be inherited from one generation to the next, altered methylation may play an important role in the hereditary nature of Alzheimer's disease.
Paula Alejandra Desplats, Ph.D., and colleagues believe DNA methylation problems may be associated with brain inflammation, a characteristic feature of Alzheimer's. Specifically, dysfunctional methylation may lead to the abnormal expression of genes that promote inflammation, a disease process observed in Alzheimer's. Moreover, such changes could begin very early in the development of Alzheimer's.
For their current effort, Dr. Desplats and colleagues will study how various inflammatory genes are affected by DNA methylation at different stages of Alzheimer's disease. This work will involve autopsied brain tissue from people with and without Alzheimer's. According to Dr. Desplats' hypothesis, methylation-related changes in inflammatory gene activity may gradually increase as dementia progresses. Thus, the results of this study could identify a novel target for diagnosing Alzheimer's and monitoring its development.