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2014 Grants - Lunnon
The Role of 5-Hydroxymethylation in the Alzheimer’s Disease Brain
Katie Lunnon, Ph.D.
University of Exeter
Exeter, United Kingdom
2014 New Investigator Research Grant
A major focus of Alzheimer’s disease research is to identify genetic factors that may increase the risk of developing Alzheimer’s disease. In addition to examining certain genes that have been conclusively linked to the disease, researchers are also studying other kinds of genetic information. The epigenome, for example, is a record of chemical modifications that turn genes “on” or “off”. Scientists now suspect that in people with Alzheimer’s disease, these modifications may become altered in ways that contribute to disease progression.
In their preliminary work, Katie Lunnon, Ph.D., and colleagues have been studying brain tissue from people who had Alzheimer’s disease to examine the links between dementia and two chemical modifications of genetic material (DNA): methylation (or the addition of methyl chemical groups) and a similar process called hydroxymethylation. This chemical modification and control of DNA processing is known as epigenetics. They found that in brain samples from individuals who had Alzheimer’s disease, methylation levels were lower in the cerebral cortex, a brain region associated with learning and memory, than in areas of the brain not associated with cognitive processes. The researchers also found low overall levels of hydroxymethylation in the brains of individuals who had Alzheimer’s disease when compared to those who were cognitively healthy.
For this current grant, Dr. Lunnon and colleagues will conduct a larger study in human brain samples to confirm and expand their earlier results. The team will use two different techniques for measuring methylation and hydroxymethylation in a brain region affected early in Alzheimer’s disease called the entorhinal cortex. They will then assess how the loss of methylation and hydroxymethylation in this brain area may be linked to subsequent dementia-related changes in the brain. The results of these studies could increase our understanding of how epigenetics may contribute to the development of Alzheimer’s disease. They could also point to novel methods for preventing, diagnosing and treating Alzheimer’s disease and related dementias.