Epigenetic Landscape' Is Protective in Normal Aging, Impaired in Alzheimer's Disease

A study published in Nature Neuroscience characterizes the epigenomic landscape of brains with Alzheimer's disease (AD), specifically in the lateral temporal lobe, reports Medical Xpress . These AD brains were compared to those in both younger and older cognitively normal controls. Changes to the way the H4K16ac protein is altered along the genome in disease versus normal aging brains may indicate sites for future drug development. Because such changes shape how genes are expressed, the location and amount of epigenetic alterations is known as the "epigenetic landscape." The comparison of younger, older, and AD brain tissue uncovered a specific class of H4K16ac modifications in AD compared to normal age-established changes in the brain. This finding intimates that certain normal aging changes in the epigenome may shield against AD and when these go wrong, a person may become predisposed to AD. "Specifically it appears that AD is not simply an advanced state of normal aging, but rather dysregulated aging that may induce disease-specific changes to the structure of chromatin — the combination of histone proteins and DNA," says the University of Pennsylvania's Raffaella Nativio. The expression of amyloid plaques and tangles occurs very late in AD development, and epigenome alterations might transpire much earlier and represent targets to attack with medications.