Study suggests safer immunization approach to Alzheimer's

Researchers at the University of Illinois at Chicago have had preliminary success with a method of immunization intended to dissolve the plaques in brain tissue that are associated with Alzheimer's disease.

When injected directly into the brain of mice, antibodies against a plaque protein retarded growth of the plaques by up to two months. No adverse side effects were found.

"By injecting the antibodies directly into the brain, we were able to circumvent the problems others have encountered in developing a vaccine for this terrible disease," said Neelima Chauhan, research assistant professor in the UIC College of Medicine.

Results of the study appear in the current issue of the Journal for Neuroscience Research.

Two methods of immunization have been tried in Alzheimer's disease. In the first, called active immunization, researchers inject the antigen itself -- pieces of the sticky beta amyloid protein that constitutes the plaques -- into patients to spur the production of antibodies that should neutralize the protein and prevent it from accumulating in brain cells.

But after success in animals, clinical trials of active immunization failed when 6 to 8 percent of the patients in the study developed meningocephalitis, an inflammation of the tissue surrounding the brain.

Passive immunization did not even succeed in animal studies. In this method, researchers inject ready-made antibodies, rather than the antigen, into the animal. But high concentrations of the antibodies are required to be effective, and the large doses were found to cause hemorrhaging and inflammation.

Aware of such problems, Chauhan tried a modified passive immunization method in laboratory mice that are used as a model for the disease. In a single injection, she delivered the antibody directly into the third ventricle, a narrow cavity located between the two hemispheres of the brain, and then examined the animals' brain tissue at one, four and eight weeks.

Since the antibody did not have to circulate throughout the mouse's body where it might be absorbed, Chauhan was able to use a smaller dose than in other passive immunization studies.

At one and four weeks, the density of amyloid protein was 67 percent less than in control animals. But by eight weeks, with no further antibody injections, the protein had again accumulated. The younger the animals were, the slower the plaques regrew.

No side effects, such as hemorrhaging or inflammation, were evident.

"The results suggest that periodic administration of antibodies directly into the brain might offer a safer method for treating Alzheimer's," Chauhan said. "The vaccine reduces the accumulation of amyloid proteins for at least four weeks, providing a window during which other treatments could be used to prevent the formation of new plaques."

Alzheimer's is an age-associated degenerative neurological disease and the leading cause of dementia in older people. An estimated 10 percent of Americans over the age of 65 and half of those over age 85 have Alzheimer's.

Currently, more than 4 million Americans suffer from the disease and the number is projected to balloon to 10 to 15 million over the next several decades. Alzheimer's is now the third most expensive disease to treat in the United States, costing close to $100 billion annually.

http://www.uic.edu/