NIH Research Matters (March 12, 2012): Early Epigenetic Effects in Alzheimer's Disease

Publication Date: 
Mon, 03/12/2012

Repression of certain gene activity in the brain appears to be an early event affecting people with Alzheimer's disease, a new study found. In mouse models of Alzheimer's disease, this blockage and its effet on memory were treatable.

Alzheimer's disease is the most common cause of dementia in older adults. It affects as many as 5.1 million Americans. A hallmark of the disease is the accumulation of a toxic protein fragment called beta-amyloid in brain nerve cells (neurons). Preventing the cognitive problems that result has been a major medical challenge.

Studies in animals have linked a process called histone acetylation in brain cells to cognitive decline. Histones are the structures around which long DNA strands are wonde to make chromosomes. When histones undergo chemical modifications such as acetylation (the addition of an acetyl group), this changes how DNA is packed and thus, how genes are read, or expressed. Such changes are called epigenetic modifications.

Drugs that increase histone acetylation can reverse cognitive decline in animal models. Most of these drugs target proteins called histone deacetylases (HDACs). However, exactly how histone acetylation affects cognition has been unknown. A research team led by Dr. Li-Huei Tsai at the Massachusetts Institute of Technology used mouse models of Alzheimer's disease to investigate. Their work was partly supported by NIH's National Institute of Neurological Disorders and Stroke (NINDS) and National Institute on Aging (NIA). The study appeared online on February 29, 2012 in Nature.

Around the time the mice began to show signs of brain cell degeneration, the researchers found, the animals had higher levels of HDAC2, but not other related HDAC proteins, in the parts of the brain involved in learning and memory.

www.nih.gov/researchmatters/march2012/03122012epigenetic.htm