Three Alzheimer’s disease researchers at Washington University School of Medicine in St. Louis have been named to the 2006 Scientific American 50, an honorary list of the year’s “prime movers” in a variety of scientific disciplines.
The magazine’s board of editors chose David Holtzman, M.D., the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology; Randall Bateman, M.D., assistant professor of neurology; and John Cirrito, Ph.D., a postdoctoral research associate in neurology and psychiatry, for the list based on their outstanding contributions to understanding how Alzheimer’s disease originates in and affects the brain. Their work is funded by the National Institute on Aging, the Alzheimer’s Association, the Washington University Alzheimer’s Disease Research Center (ADRC), the Hope Center for Neurological Disorders, the Blanchette Hooker Rockefeller Fund and the Cure Alzheimer’s Fund.
The list will appear in the December issue of the magazine, due out on Nov. 21.
Earlier this year, Bateman and Holtzman led a multidisciplinary team of scientists that developed the first safe and effective method for assessing production and clearance of amyloid beta peptide (Abeta) in the human central nervous system.
Scientists have long recognized increased Abeta levels in the brain as a characteristic and likely causative factor in Alzheimer’s disease. The new test will help answer a question that has frustrated Alzheimer’s researchers for decades: do patients have high levels of brain Abeta because their brains make too much of it or because they fail to clear it out quickly enough?
Because Alzheimer’s symptoms take many years to develop, some researchers had assumed that the creation and clearance rates for Abeta were very slow. But the initial test of the new technique, applied to six healthy volunteers, suggested the opposite.
“Abeta has the second-fastest production rate of any protein whose production rate has been measured so far,” Bateman said. “In a time span of about six or seven hours, you make half the Abeta found in your central nervous system.”
Ideally, the production and clearance rates stay balanced, causing the overall amount of Abeta in the central nervous system to remain constant. In the healthy volunteers who were the first test subjects, Bateman found the production and clearance rates were the same. He is now applying the technique to individuals with Alzheimer’s disease.
The new test should also be helpful in efforts to diagnose Alzheimer’s disease earlier and to test new treatments. It was developed in collaboration with Kevin E. Yarasheski, Ph.D., associate professor of medicine and assistant director of the Washington University Biomedical Mass Spectrometry Resource and with the support of the ADRC, which is directed by John C. Morris, M.D., the Friedman Distinguished Professor of Neurology.
Factors affecting Abeta accumulation are also a key issue for Cirrito, the other WUSTL researcher in the Scientific American 50. Cirrito modified an existing technique called microdialysis to enable repeated sampling and measurement of Abeta levels in the brains of mice genetically altered to model human Alzheimer’s disease. In a paper published in late 2005, Cirrito, his postdoctoral mentors Holtzman and Steven Mennerick, Ph.D., associate professor of psychiatry, and others used direct electrical stimulation and a variety of injected compounds to turn nerve cell communication up and down in the brains of living mice. Once every 30 minutes, they assessed the effect these changes in brain cell activity had on Abeta levels.
They found that turning up brain cell firing rates drove up levels of Abeta in the spaces between brain cells. Corresponding drops in Abeta levels occurred when brain cells’ ability to send messages was dampened or blocked completely.
The study’s results may help explain why specific brain regions are vulnerable to Alzheimer’s. Noting earlier studies that suggested crossword puzzles, exercise and other mental stimulation can reduce the chances of developing Alzheimer’s disease, Holtzman and Cirrito speculated that those tasks increase activity in brain areas unlikely to be damaged by Alzheimer’s. They also simultaneously may be causing a corresponding activity reduction in brain regions consistently damaged by the disease.
“Almost all neurological diseases involve selective vulnerability—only certain classes of nerve cells or nerve cells found in particular brain regions are affected,” Holtzman said. “Why that vulnerability is so selective often can be very difficult to determine, and Alzheimer’s disease is no exception.”
Washington University School of Medicine’s full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.