David Holtzman: Attacking Alzheimer's With a New Test for Amyloid Beta

June 30, 2009, U.S. News and World Report

Neuroscientist David Holtzman was captivated by Alzheimer's disease as a medical student. Now the 47-year-old associate director of the Alzheimer's Disease Research Center at the Washington University School of Medicine in St. Louis, Holtzman says he realized that Alzheimer's "was going to be one of the biggest problems that we would face, and it was unsolved." Figuring out how the illness begins and how to prevent or slow it has been his goal ever since.

Holtzman's persistence is paying off. Until now, it typically took about two years to determine whether a new Alzheimer's drug was having an effect. But recently, he and colleagues devised a test that rapidly shows whether an experimental medication has a chance of working. "There aren't good ways without doing a long, expensive trial" to determine this, he says. But with the new test, called stable isotope-linked kinetics, or SILK, "we were able to come up with a technique to figure out over a day or two whether a drug is hitting its target in the brain," he says.

SILK reveals whether the medication is limiting production of amyloid beta, a substance that can lead to the formation of plaques on the brains of Alzheimer's patients. The test is the first that directly measures the rate at which amyloid beta is produced and how quickly it is cleared from the brain. Small amounts of amyloid beta are generated as an ordinary metabolic byproduct and are believed to do no harm, but larger amounts seem to be tied to Alzheimer's.

His lab also is investigating how to manipulate the most important genetic risk factor for Alzheimer's, a protein called APOE, in hopes of treating the disease. "He's clearly one of the leaders in Alzheimer's disease research," says Stephen Snyder, deputy director of the division of neuroscience at the National Institute on Aging. "He's really sort of set a pace, a research agenda."

Holtzman, who also chairs the medical school's neurology department, would prefer not to focus on treating the disease. His greatest hope is for researchers to recognize that the disease "starts before the symptoms and signs." That way, he says, "we can work on prevention."