Alzheimer's is the cruelest of the diseases that strike the elderly. There is no known cure for this neuro-degenerative disorder that eats away the body's command center, first stealing memory, then bodily functions, and ultimately life as it runs its course over five to 15 years. It holds five million people hostage - most of them past age 70 - and ranks 4th in cause of death for Americans. It is estimated that 10 percent of people past age 65 develop Alzheimer's, a number that rises to 50 percent by age 85.

It is the most expensive illness society must shoulder, with direct and indirect costs reaching more than $100 billion a year. By the year 2050, Alzheimer's could claim upwards of 15 million victims and easily quadruple the financial burden to society.

Except for a small sub-set of the population with an inherited genetic mutation that causes the disease, most Alzheimer's is not related to family history and the cause is not known. To be sure, studies show that there are outside factors that increase the risk of developing the disease. Boxers, for example, run a higher risk than someone who has not had head injuries. And post-menopausal women who do not take estrogen are more likely to develop Alzheimer's than those who do, says Dr. John Trojanowski, co-director with his wife Virginia M-Y Lee of the Center for Neurodegenerative Disease Research at University of Pennsylvania. He also is director of the Alzheimer's Disease Center at Penn.

The hallmark signatures of Alzheimer's are brain lesions of abnormal, insoluble protein deposits called amyloid plaques, and neurofibrillary tangles. It's thought that the lesions occur when normal brain substances run amok and convert into hair-like threads that subsequently clump into a confused mess of tangles and snarls in the brain. As brain cells stop talking to one another, they atrophy, causing memory and reasoning to fade. The best drugs currently available to combat Alzheimer's are only modestly effective, he says. Better therapies are in the research pipelines and include clinical trials already underway that involve immunization.

Considerable research is focused on ways to block the enzymes necessary for the production of the brain deposits, or to find "plaque-busting" agents that can wipe them out after they are formed.

Current research "has a strong shot at making a difference five years from now in the treatment of Alzheimer's," predicts Dr. Trojanowski, who will showcase the latest research at a day-long conference at the Center for Neurodegenerative Disease Research at University of Pennsylvania on November 7. (Please contact Gayle Viale, assistant to Dr. Trojanowski, at 215.662.4708 or viale@mail.med.upenn.edu, for more information about the conference. Deadline for registering is October 1, 2001.)

There is still some doubt, but scientists generally believe that a substance called A beta amyloid is the catalyst that promotes the manufacture and clumping of abnormal deposits in Alzheimer's brains. Scientists made a giant leap with discovery of the two enzymes that produce A beta amyloid.

The theory in some scientific circles is that if you can block either or both you can reduce the production of A Beta, which may delay and prevent the onset of Alzheimer's.

A number of pharmaceutical companies are working on inhibitors of the two enzymes. Elan Corporation is in clinical trials testing an antibody approach. Dr. Ivan Lieberburg, an Elan researcher, doesn't buy into the theory that Alzheimer's patients make too much beta amyloid. He thinks they can't clear it fast enough. His vaccination produces anti-bodies that trigger a response in brain cells to clear away debris. Once the amyloid is tagged with the antibody, they can detect it, consume it and clear it away.

"It works very well in mice," he says. "If we immunize mice before they develop the disease, remarkably no beta amyloid occurs in brains of animals that are immunized. So we actually prevent the disease from occurring in these animals. In animals that have already developed moderate Alzheimer's, the antibodies can halt and in some cases reverse it. It always works on animals. But mice are not men, and we do not know what will happen in people. If we see anything remotely resembling the results with mice, it would be a dramatic breakthrough for Alzheimer's therapy."

In a variation on immunization therapy, the Center for Neurologic Diseases at Brighman and Women's Hospital is working on nasal vaccines because they are easier for caregivers to administer. When they used an immune booster, they got dramatically increased antibody production and significant reduction of plaques, according to Dr. Cynthia Lemere. They also made the unanticipated discovery of increased amyloid in the bloodstreams of the dosed mice, suggesting that the antibodies were pulling the damaging substance from the brain and holding it in the bloodstream where it was targeted for clearance.

While a cure for Alzheimer's is still eluding science, researchers believe they are getting closer to finding the magic bullet that will stop the brain plaques and tangles from growing in the first place.