BOSTON, Feb 28, 2001 (United Press International via COMTEX) -- A new study in mice suggests that the plaques, or protein deposits, associated with Alzheimer's Disease can be cleared from the brain -- and more easily than most scientists had ever imagined. Applying an anti-plaque vaccine directly against the brain of the mice, through holes bored in their skulls, researchers at Massachusetts General Hospital in Boston, were able to clear 70 percent of the plaques in just three to eight days.

The plaques are composed of a protein, amyloid-beta, which -- researchers increasingly agree -- appears to be a causative factor in the development of Alzheimer's disease. Recent studies have suggested that vaccination with amyloid-beta can provoke an antibody response that helps prevent the formation of plaques. However, the new study, published in the March issue of Nature Medicine, represents the first successful effort to clear pre-existing plaques with anti-amyloid antibodies.

Tracking and determining the role of plaques in Alzheimer's has been elusive because no has, until today, been able to observe the plaques in a living animal. Yet Dr. Bradley Hyman, a neurologist and chief author on the Nature Medicine paper, was able to visualize individual plaques through a new multi-photon microscope, which permits deeper and more precise imaging within tissue.

"The first really exciting part of our work was simply being able to see the plaques." Hyman said.

Using fluorescent tracers applied to the brain, he and his team were able to track the natural history of individual plaques before and after the vaccine was introduced.

Although the majority of plaques were cleared, no one knows whether the effect is a lasting one. Hyman and his colleagues are now pursuing a follow-up study in which the mice will be evaluated periodically even after plaques have been cleared, to see if the deposits build up again.

The technology Hyman is using is a milestone in itself, according to Dr. Dale Schenk, Vice President of Discovery Research for Elan Pharmaceuticals, which collaborated with Hyman. "What he's done with the multi-photon microscope has broad implications for the study of any disease in a mouse model, in which there is pathology in the brain," said Schenk.

The role that plaques play in the disease in human remains a point of controversy among Alzheimer's researchers.

Preliminary studies in mice published last year suggested that the reduction of plaques could improve the cognitive performance of lab mice, but Hyman did not explore this correlation in the current work.

"Plaques may be the body's successful way of coping with the disease," said Dr. Ashley Bush, associate professor of psychiatry at Harvard University Medical School. Bush is one of a group of researchers who believe that amyloid-beta is more dangerous in its soluble form rather than in plaques. Nonetheless, he acknowledges the remarkable speed with which plaques were removed in the Mass General study. "It proves that the plaques are not sitting there like cement. They were cleared quite easily," he said.

The experiment suggests one more strategy toward reducing the overall load of amyloid beta, which most investigators believe, one way or another, produces the cognitive deterioration in Alzheimer's disease..

"Certainly this study is consistent with others that show that stimulating the immune system can clear amyloid beta," said Bill Thies, Vice-President for Medical and Scientific Affairs for the National Alzheimer 's Association. "Antibodies that are the same as those being generated by the vaccines now in human trials helped remove plaques in the mice."

Thies stresses that while vaccine studies offer potential hope for successfully preventing or treating Alzheimer's, vaccines may carry potential risks, too, and so other strategies need to be pursued. Most other treatments currently under investigation are also anti-amyloid-beta therapies, whether they are designed to reduce the protein's presence, prevent its formation or reduce the so-called oxidative damage with which it is often linked.

(Reported by Katie Leishman in Los Angeles, Calif.)

By UPI Science News

Copyright 2001 by United Press International.

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