New clue to Alzheimer's discovered

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 there long has been a question whether this is a cause of the disease or a side effect. Also involved are tangles of a protein called tau; some scientists suspect this is the cause.

Now, researchers have caused Alzheimer's symptoms in rats by injecting them with one particular form of beta-amyloid. Injections with other forms 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 a team led by Dr. Ganesh M. Shankar and Dr. Dennis J. Selkoe of Harvard Medical School were reported in Sunday's online edition of the journal Nature Medicine.

The researchers used extracts from the brains of 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 brains of rats. 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. Studies were also done on mice and 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 that are essential for communication between them.

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 of the three types had an effect, she said in a telephone interview.

Morrison-Bogorad said the findings may help explain the discovery of plaque in the brains of people who do not develop dementia. For some time, doctors have wondered why they find some brains in autopsy that are heavily coated with beta-amyloid, but the person did not have Alzheimer's.

The answer may lie in the two types of beta-amyloid that did not cause symptoms.

Now, the question is why one has the damaging effect and not others.

"A lot of work needs to be done," Morrison-Bogorad said. "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."

Dr. Richard J. Hodes, director of the National Institute on Aging, said that "while more research is needed to replicate and extend these findings, this study has put yet one more piece into place in the puzzle that is Alzheimer's."

In addition to the Institute on Aging, the research was funded by Science Foundation Ireland, Wellcome Trust, the McKnight and Ellison foundations and the Lefler Small Grant Fund.