Telltale sign: Amyloid plaques on an Alzheimer’s patient’s brain. Protein can reawaken in older brains and help to prevent dementia.

New York Times,

Protein may hold the key to who gets Alzheimer's

  • Article by: PAM BELLUCK
  • New York Times
  • March 29, 2014 - 4:45 PM

It is one of the big scientific mysteries of Alzheimer’s disease: Why do some people whose brains accumulate the plaques and tangles so strongly associated with Alzheimer’s not develop the disease?

Now, research at Harvard suggests a possible answer that could lead to new treatments.

The memory and thinking problems of Alzheimer’s disease and other dementias, which affect an estimated 7 million Americans, may be related to a failure in the brain’s stress response system, the new research suggests. If this system is working well, it can protect the brain from abnormal Alzheimer’s proteins; if it gets derailed, key areas of the brain start degenerating.

“This is the first study that is really starting to provide a plausible pathway to explain why some people are more vulnerable to Alzheimer’s,” said Li-Huei Tsai of the Picower Institute for Learning and Memory at the Massachusetts Institute of Technology.

The research, published in the journal Nature, focuses on a protein previously thought to act mostly in the brains of developing fetuses. The scientists found that the protein also appears to protect neurons in healthy older people from aging-related stresses. But in people with dementias, the protein is sharply depleted.

Experts said the role of the protein, called REST, could spur development of new drugs for dementia.

REST, a regulator that switches off certain genes, is known to keep fetal neurons in an immature state until they develop to perform brain functions, said Dr. Bruce A. Yankner, a genetics professor at Harvard Medical School and the lead author of the new study. By the time babies are born, REST is mostly inactive.

Researchers were startled to find that REST was the most active regulator in older brains.

They hypothesized that it was because in aging, as in birth, brains encounter great stress. REST appears to switch off genes that promote cell death, protecting neurons from normal aging processes.

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