Two new NIH-supported studies have shown that a person’s epigenome—the chemical modifications, or marks, on our DNA that turn gene activity on and off—may influence Alzheimer’s disease-related changes in the brain. The two groups of researchers examined brain tissue donated by volunteers with Alzheimer’s and those free of the disease and linked a specific epigenome marker, DNA methylation, with Alzheimer’s pathology in the brain. Because the epigenome can be affected by lifestyle and the environment, these findings may offer new targets for therapies to delay, prevent or treat Alzheimer’s disease.
The independently-run, epigenome-wide association studies (EWAS) reported online in Nature Neuroscience on August 17, 2014, were led by: Philip L. De Jager, M.D., Ph.D., Brigham and Women's Hospital, Boston, in collaboration with co-author David Bennett, Ph.D., Rush University Medical Center, Chicago; and by Jonathan Mill, Ph.D., of the University of Exeter Medical School and King’s College London, in collaboration with colleagues in the United Kingdom and United States.
Because the epigenome determines gene expression—that is, which genes are active and what proteins they produce—it can impact health and longevity. These new studies show for the first time that DNA methylation may impact specific gene regions, several of which are thought to play a role in Alzheimer’s disease risk, onset and progression.
De Jager PL., et al. Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci. Nature Neuroscience, published online Aug. 17, 2014; DOI:10.1038/nn.3786
Lunnon K., et al. Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease. Nature Neuroscience, published online Aug. 17, 2014; DOI:10.1038/nn.3782