Researchers have demonstrated in rats that injections of a naturally occurring brain hormone can block a type of cell degeneration seen in Alzheimer's disease, thereby opening the door to potential treatment of the degenerative neurological disorder, which is the fourth leading cause of death in the United States.
The Boston scientists have shown for the first time in live animals that accumulation of a common brain protein called beta-amyloid causes the nerve damage characteristic of Alzheimer's, for which there is now no good therapy, and that it is possible to prevent such damage.
The study, being published in today's Proceedings of the National Academy of Sciences, is the most recent of several that have brought researchers close to identifying the precise cause of the disorder and to developing new therapies.
"Having the capacity to test potential treatments in animals represents a long-awaited victory in the battle against Alzheimer's disease," said neurologist Zevan Khachaturian of the National Institute on Aging.
"We're very excited about this and hope other people will follow up on it," said neurologist Creighton Phelps of the Alzheimer's Association. "We're getting right to the heart of the matter, that beta-amyloid seems to be playing a very key role in Alzheimer's. We can't say it's the cause quite yet, but if we can block it, we may very well be able to slow down or stop the progression of the disease."
Neurologist Bruce A. Yankner of Boston Children's Hospital, the principal investigator in the new study, said that members of the research team were studying the effects of the brain hormone, called substance P, in other animals, including primates, and that they might begin studying the material in humans within five years.
Alzheimer's disease is characterized by memory loss, disorientation, depression and deterioration of bodily functions. The National Institute on Aging says the disease affects about 4 million Americans and causes 100,000 deaths annually. The average time between diagnosis and death is eight years.
The most noticeable biological sign of Alzheimer's is the presence of protein plaques in the regions of the brain that control memory and learning. The primary component of these plaques, which are observable only in an autopsy, is beta-amyloid.
Neurologists have long debated whether the plaques are the cause of Alzheimer's or simply a byproduct of some unknown disease process. But a growing body of evidence is implicating the plaques as a cause.
Last fall, Dr. Yankner and molecular biologist Rachael Neve of the University of California, Irvine, independently reported that beta-amyloid caused the degeneration of brain cells grown in the laboratory. In April, biochemist Eugene Roberts of the City of Hope in Duarte, Calif., reported that injecting beta-amyloid into the brains of mice caused them to forget recently learned tasks.
Now, Dr. Yankner and his colleagues at Massachusetts General Hospital and the University of Alaska have shown that injections of beta-amyloid into rat brains cause the death of cells near the injection site, seemingly closing the circle. The team has not had time to study the effects of the injections on the animals' behavior, a necessary step in proving that the protein causes the disorder.
That proof is expected to come from studies of two new strains of genetically engineered mice, reported last month, that develop beta-amyloid plaques in their brains. But those mice, which have reached only middle age, have not been studied long enough to determine whether they develop mental impairment as a result of the plaque formation.