2013-2014 Alzheimer’s and Related Diseases Research Award*Remodeling of DNA Methylation Associated with Increased Beta Amyloid Deposition in Mice
*The Virginia Center on Aging which administers the Alzheimer’s and Related Diseases Research Award Fund for the Commonwealth of Virginia, provides seed money to researchers in Virginia to stimulate innovative research into biomedical and psychosocial aspects of dementia, including cell biology, caregiving, and animal modeling.
Remodeling of DNA Methylation Associated with Increased Beta Amyloid Deposition in Mice
Gary Isaacs, PhD
Although several mutations have been associated with patients suffering from AD, several lines of evidence suggest that AD development might be caused by chemical modifications of the base DNA sequence (e.g., cytosine methylation, cytosine hydroxymethylation). Our project seeks to identify regions of the genome that become epigenetically altered as cells progress toward an AD-like state. To this end, the investigators plan to use DNA microarrays to map the locations of both cytosine methylation and cytosine hydroxymethylation in an AD mouse model system. Mice expressing two AD-related transgenes will serve as our AD-like condition, while mice lacking the transgenes will serve as our AD control group. The transgene positive mice produce more beta amyloid plaques than control mice, they do significantly worse on cognitive function experiments, and die at a younger age. This model is by far better than human cell culture models that utilize immortalized cell lines and exogenous treatment of purified amyloid beta. Our approach to identify AD-related epigenetic changes on a genomic scale represents a novel application of current technology to the realm of AD biology.
(Dr. Isaacs may be contacted at 434/582-2224, firstname.lastname@example.org)
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