Researchers Identify Epigenetic Drivers for Late-Onset Alzheimer’s Disease

New findings suggest that late-onset Alzheimer's Disease is driven by epigenetic changes--how and when certain genes are turned on and off--in the brain. The results were published online on September 28, 2020 in Nature Genetics. The article is titled “An Integrated Multi-Omics Approach Identifies Epigenetic Alterations Associated with Alzheimer’s Disease.” Research led by Raffaella Nativio, PhD, a former Research Associate at Epigenetics, Shelley Berger, PhD, a Professor of Genetics, Biology and Cell and Developmental Biology and Director of the Epigenetics Institute, and Nancy Bonini, PhD, a Professor of Biology and Cell and Developmental Biology, all in the Perelman School of Medicine at the University of Pennsylvania, used post-mortem brain tissue to compare healthy younger and older brain cells to those with Alzheimer's Disease. The team found evidence that epigenetic regulators disable protective pathways and enable pro-disease pathways in those with the disease. "The last five years have seen great efforts to develop therapeutics to treat Alzheimer's disease, but, sadly, they have failed in the clinic to treat humans suffering from this horrible disease," Dr. Berger said. "We are trying a completely different approach to reveal the critical changes in brain cells, and our findings show epigenetic changes are driving disease." Epigenetic changes alter gene expression without DNA mutation, but rather by virtue of marking proteins that package and protect DNA, called histones. Dr. Berger added, "the activity of epigenetic regulators can be inhibited by drugs, and hence we are excited that this may be an Achilles' heel of Alzheimer's that can be attacked by new therapeutics."
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