Study Suggests New Targets for Drug Studies

Alzheimer's Association
Friday, 5 December 1997

Researchers report the discovery of a protein that may accelerate the formation of abnormal deposits in the brains of people with Alzheimer's disease, the prevention of which may slow down or even prevent the disease, according to the Alzheimer's Association.

"We're very enthusiastic about the findings of this study, " said Zaven Khachaturian, Ph.D., director of the Association's Ronald & Nancy Reagan Research Institute. "We are beginning to tie together the various pieces of our knowledge of Alzheimer's disease. It is through this type of research that our knowledge of the disease will significantly advance. "

Khachaturian added that the findings need to be replicated and confirmed by other scientists before we can be certain of their validity.

"Amyloidogenic role of cytokine TGF-b 1 in transgenic mice and in Alzheimer's disease, " appears in the October 1997 issue of Nature. The study was funded, in part, by the Alzheimer's Association. Other funders include the National Institutes of Health and the Swiss National Science Foundation. In the study, researchers at the J. David Gladstone Institutes and the Universities of California at San Francisco and San Diego, led by Lennart Mucke, M.D., report that a protein, transforming growth factor b 1 (TGF-b 1), accelerates the development of amyloid deposits around blood vessels in the brains of mice. Normally, TGF-b 1 plays an important role in the brain's response to injury. Hard deposits, called plaques, made of an abnormal protein called amyloid-beta peptide, are found on the brains of people with Alzheimer's disease. Some scientists think the plaques cause brain cells to die in Alzheimer's.

According to Khachaturian, if confirmed, TGF-b 1 would be one of a growing number of substances that modify the amount of amyloid in a person's brain. Another such modifier is apoE, the protein encoded by the APOE gene, which is an established risk factor for late-onset Alzheimer's disease.

"This finding is exciting in that it may broaden the number of potential targets for Alzheimer drug therapies, " said Khachaturian. "We can focus our attention not only directly on amyloid, but also on these modifiers. For example, if we can reduce TGF-b 1, we may be able to reduce the deposits of amyloid. "

"The widely reported preliminary connections we've seen between use of non-steroidal anti-inflammatory drugs, such as ibuprofen, and Alzheimer's indicated to scientists that inflammatory mechanisms are somehow involved in Alzheimer's disease, but we don't know quite how yet, " Khachaturian said. "This study begins to shed light on the involvement of the brain's inflammatory and repair response systems in Alzheimer's disease, and their possible connection to one of the two well-known Alzheimer lesions, amyloid plaques. "

For more information, or to contact Alzheimer's Association, see their website at: www.alz.org