March 2, 2001

Lab mice bred to develop the senile plaques, or deposits, of Alzheimer's disease in a recent MGH study had a majority of their plaques disappear three to eight days after treatment with anti-plaque antibodies. MGH researchers, working with scientists at Elan Pharmaceuticals, cleared 70 percent of plaques by applying the antibodies directly to the mice's brains. Their findings appear in the March issue of Nature Medicine.

A year and a half ago, Elan scientists demonstrated that they could prevent plaque formation in the Alzheimer's-prone mice by vaccinating them with a protein found in the plaques, called amyloid-beta. But this is the first time that anyone has been able to clear pre-existing plaques in a living animal, explains Bradley Hyman, MD, PhD, an MGH neurologist and senior author of the study.

"No one has ever directly demonstrated the clearance of amyloid-beta deposits," says Brian Bacskai, PhD, an assistant in Neurology at MGH and lead author of the study. "This was an especially surprising process because it was so rapid. It really took only a few days for what looks to be almost complete clearance of amyloid-beta deposits."

The experiments signify another achievement: This is the first time that anyone has observed senile plaques in a living animal. Too minute to be imaged by conventional noninvasive methods such as magnetic resonance imaging (MRI) and computed tomography (CT), plaques have been observed only by microscopic examination of postmortem brain samples. The MGH team made its observations on the living animals using a newly invented device called a multi-photon microscope.

"With our ability to image the plaques, we could clearly determine what happens to plaques before and after treatment with anti-amyloid-beta antibodies," says Bacskai.

Although it still is too early to know whether this result will one day apply to treatment of human patients, the MGH scientists see it as an important pair of proof-of-principles. First, Alzheimer's plaques can be reversed. Second, the plaques can be reversed by the external application of antibodies rather than by internally mustering up the immune army of T cells and B cells, as is done through a vaccination.

Funding for this study was provided by the National Institute on Aging, an Alzheimer Association Pioneer Award and the Walters Family Foundation.