Study Details New Molecular Approach to Preventing Alzheimer's
April 25 -- THURSDAY, April 24 (HealthDay News) -- German researchers are reporting a new approach to the possible prevention of the molecular "debris" that's associated with the development of Alzheimer's disease.
The basic idea -- to block the activity of an enzyme called beta-secretase -- is not new, said study lead author Dr. Kai Simons, a professor of cell biology at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden.
A number of laboratories, both academic and commercial, are working on methods to prevent the enzyme from slicing a protein into beta amyloid fragments that form the brain plaques found in people with the disease. All work on the same principle. "If we decrease the amount of cleavage, we could in all likelihood reduce the likelihood of the disease," Simons said.
Most experts now agree that formation of the beta amyloid plaques is directly linked to the development of Alzheimer's. The problem with most proposed methods of blocking beta-secretase, Simons said, is that they are designed to work outside of the affected brain cells.
"This process of cleaving takes place inside cells," he said. "We have constructed an inhibitor which binds outside, on the cell membrane, and goes into the cell where the cleavage occurs."
Reporting in the April 25 issue of the journal Science, Simons and his colleagues described both test-tube experiments and animal studies in which the combination of an anchoring molecule and a beta-secretase inhibitor reduced the formation of beta amyloid plaque by more than 50 percent over four hours, while the inhibitor alone was ineffective.
The success is just one small step toward a medically useful preventive therapy for Alzheimer's disease, Simons acknowledged. For one thing, the treatment was given by injection into the brains of the experimental animals (fruit flies and mice), something not likely to be done with people.
"This is proof of principle," Simons said. "The idea would be to get it into the blood in humans and then over the blood-brain barrier into the brain. There are many ways for molecules to get into the brain."



