“Epigenetic Landscape” is Protective in Normal Aging, Impaired in Alzheimer’s Disease

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Although certain genetic variants increase the risk of Alzheimer’s disease (AD), age is the strongest known risk factor. But the way in which molecular processes of aging predispose people to AD, or become impaired in AD remains a mystery.

A team of researchers from the Perelman School of Medicine at the University of Pennsylvania profiled the epigenomic landscape of AD brains, specifically in one of the regions affected early in AD, the lateral temporal lobe. They compared these to both younger and elderly cognitively normal control subjects. The team described the genome-wide enrichment of a chemical modification of histone proteins that regulates the compaction of chromosomes in the nucleus (called acetylation of lysine 16 on histone H4, or H4K16ac for short).

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Changes to the way H4K16ac is modified along the genome in disease versus normal aging brains may signify places for future drug development. Because changes in H4K16ac govern how genes are expressed, the location and amount of epigenetic alterations is called the “epigenetic landscape.”

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