March 1, 2001 -- For the first time, researchers have shown that one of the hallmarks of Alzheimer's disease -- sticky deposits of an abnormal protein called beta-amyloid -- can be cleared from the brains of living animals. Their finding suggests that the human immune system could be trained to help reverse or prevent at least some of the damage this protein does to the brains of people with Alzheimer's disease.
"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," according to a statement by one of the researchers, Brian Bacskai, PhD, a neurologist at Massachusetts General Hospital in Boston.
The study also shows that a new imaging device called a multiphoton microscope can provide images of the protein deposits in the brains of living creatures. Until now, the only way to confirm the presence of these deposits and to diagnose Alzheimer's with 100% accuracy has been after death, by direct examination of the brain at autopsy.
Beta-amyloid protein forms clumps in the brain known as senile plaques, and these have long been implicated in Alzheimer's disease. Researchers do not know for certain, however, if the plaques are themselves responsible for the devastating memory losses associated with the disease, or whether they occur as a result of some other aspect of the disease.
For this reason, researchers aren't sure whether clearing plaques from the brain actually will help patients much.
"It will be tremendously interesting to see whether in fact cognitive function does improve," says Margaret Esiri, MD, a neuropathologist at the University of Oxford, U.K., who reviewed the study for WebMD.
The problem, she says, is that while the mice used in the study have a genetic mutation that causes them to develop amyloid plaques similar to those seen in Alzheimer's disease, their brains do not exhibit other features of the disease, such as abnormal tangles of nerve fibers.
"The tangles are the thing that we know correlates very closely with how demented you are," she says, so the mouse developed displays only part of the disease as seen in humans.
Bacskai and his colleagues originally undertook the study, reported in the March issue of the journal Nature Medicine, to test whether the multiphoton microscope could show evidence of amyloid deposits in the brains of living animals. Not only were they able to see the deposits, but they also found something potentially far more exciting.
In order to make the amyloid deposits stand out visually, the researchers first stained them in such a way that they would glow when exposed to a certain kind of light. Later on, they did the same thing to antibodies especially designed to fight against amyloid plaques.
What the researchers discovered was that while 80% of the amyloid plaques seen in the brains of the untreated animals could still be seen under the microscope, only about 30% of the plaques in the antibody-treated mice could be detected.
In addition, the remaining pockets of amyloid protein in the antibody-treated mice were surrounded by immune system mop-up cells, suggesting that the antibodies helped to fortify the body's own defenses in the fight against the plaques.
Boosting the immune system with antibodies might be an effective way to prevent beta-amyloid from accumulating in the brain -- as well as a way to clear it up once Alzheimer's disease has set in -- the data seem to suggest. And the approach could be especially effective in the elderly, who often lack a strong immune-system response.