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Researchers link a type of protein, Alzheimer's characteristics

Injections cause symptoms in rats

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Associated Press / June 23, 2008

WASHINGTON - Researchers have uncovered a new clue to the cause of Alzheimer's disease.

The brains of people with the memory-robbing form of dementia are cluttered with a plaque made up of beta-amyloid, a sticky protein. But it has long been questioned whether this is a cause of the disease or a side effect. Also involved are tangles of a protein called tau, and some scientists suspect this is the cause.

Now, researchers have caused Alzheimer's symptoms in rats by injecting them with a particular form of beta-amyloid. Other types of beta-amyloid did not cause illness, which may explain why some people have beta-amyloid plaque in their brains but do not show disease symptoms.

The findings by the team, led by Dr. Ganesh M. Shankar and Dr. Dennis J. Selkoe of Harvard Medical School, were reported in yesterday's online edition of the journal Nature Medicine.

The researchers used brain extracts from people who donated their bodies to medicine.

Forms of soluble beta-amyloid containing different numbers of molecules, as well as insoluble cores of the brain plaque, were injected into the mice. There was no detectable effect from the insoluble plaque or the soluble one-molecule or three-molecule forms, the researchers found.

But the two-molecule form of soluble beta-amyloid produced characteristics of Alzheimer's in the rats, they reported.

Those rats had impaired memory function, especially for newly learned behaviors. When their brains were inspected, the density brain cells were reduced by 47 percent. The beta-amyloid seemed to affect synapses, the connections between cells.

The research, for the first time, showed the effect of a particular type of beta-amyloid in the brain, said Dr. Marcelle Morrison-Bogorad, director of the division of neuroscience at the National Institute on Aging, which helped fund the research. It was surprising that only one type had an effect, she said in a telephone interview.

Morrison-Bogorad said the findings might help explain plaque in the brains of people who do not develop dementia.

The answer may lie in the beta-amyloid that did not cause symptoms. "Nature keeps sending us down paths that look straight at the beginning, but there are a lot of curves before we get to the end," Morrison-Bogorad said.

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