Busy brains and Alzheimer's

Cells talk more in areas Alzheimer's hits first, boosting plaque component

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Could a crossword a day keep Alzheimer’s away?

Higher levels of cell chatter boost amyloid beta in the brain regions that Alzheimer’s hits first, School of Medicine researchers report. Amyloid beta is the main ingredient of the plaque lesions that are a hallmark of Alzheimer’s.

These brain regions belong to a network that is more active when the brain is at rest. The discovery that cells in these regions communicate with each other more often than cells in other parts of the brain may help explain why these areas are frequently among the first to develop plaques.

Working with mice genetically engineered to develop Alzheimer’s-type brain changes, scientists reduced the size and number of plaques by decreasing brain cell activity in certain regions.

The results, which appeared in the May 1, 2011 issue of Nature Neuroscience, are the latest to hint at a resolution to lines of evidence that have suggested busier brain cells can both contribute to and prevent Alzheimer’s. According to a new theory, just which brain cells are kept busy may make all the difference.

“Engaging the brain in tasks like reading, socializing or studying may be helpful because they reduce activity in susceptible regions and increase activity in regions that seem to be less vulnerable to Alzheimer’s plaque deposition,” says David M. Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. “I suspect that sleep deprivation and increased stress, which may affect Alzheimer’s risk, may also increase activity levels in these vulnerable regions.”

The susceptible regions of the brain highlighted in the new study belong to the “default mode network,” a group of brain regions that become more active when the brain is not engaged in a cognitively demanding task.

Study co-author Marcus E. Raichle, MD, professor of neurology, of radiology and of neurobiology, was among the first to describe the default mode network. In a 2005 paper, Washington University researchers showed that regions in the default mode network are often among the first to develop Alzheimer’s plaques.

According to Holtzman, the new study’s results demonstrate the direct connection between amyloid plaque formation and growth and changes in brain cell activity levels in various parts of the brain. He plans further investigations of the mechanisms that regulate default brain activity, their connections to phenomena such as sleep, and their potential effects on Alzheimer’s disease.

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