Alzheimer Researchers Focus on Plaque Buildup in Brain; Advances in Understanding Process Hold Promise for Testing Amyloid Hypothesis

7/23/2002

From: Elizabeth Wilson or Jim Prescott, 312-335-4078 (Chicago) or 46-872720-05 (Stockholm, July 20-25), both of the Alzheimer's Association (USA) E-mail: media@alz.org

STOCKHOLM, Sweden, July 23 -- Significant advances in our understanding of how amyloid plaques form in the brain are providing researchers with new opportunities to study what causes Alzheimer's disease and what we can do to treat or prevent it.

Plaques are made mostly of protein fragments called beta amyloid and are found in the spaces between nerve cells in the brains of people with Alzheimer's. While researchers still do not know what causes Alzheimer's, it is widely believed that the production of amyloid plaques is a central feature of the disease.

"Much of the most promising Alzheimer research is looking at how we can reduce the buildup of amyloid plaques in the brain," said Alzheimer's Association Vice President of Medical and Scientific Affairs William Thies, Ph.D. "The more we learn about how to interfere with the creation of beta amyloid, the closer we come to determining whether this is the right approach to fighting Alzheimer's."

A promising study presented at the 8th International Conference on Alzheimer's Disease and Related Disorders this week focuses on a way of reducing amyloid plaque buildup in the brains of mice that have been genetically altered to develop amyloid. Beta amyloid is clipped from a larger protein in a two-step process involving enzymes called beta secretase and gamma secretase. Patrick May of Eli Lilly and Co., along with Elan Pharmaceuticals, Inc., identified a compound that inhibits the function of gamma secretase.

These researchers treated transgenic mice over a 90-day period when they would normally be accumulating large amounts of amyloid in their brains. Treating the mice with the gamma secretase inhibitor produced an 80-90 percent reduction in the level of beta amyloid without any adverse reactions.

Earlier this year, clinical tests of a potential vaccine designed to create antibodies to beta amyloid and thereby increase the disappearance of the amyloid were halted when some participants developed inflammation of the central nervous system.

"It is encouraging to see another approach to reducing amyloid buildup," said Thies. "Additional research will be necessary to replicate the findings and reproduce them in other animals and eventually in humans.

"Thousands of researchers are seeking to understand the brain abnormalities first discovered by Dr. Alzheimer in 1906," said Thies. "While we have made tremendous progress, we still have a long way to go before we can say we have conquered this devastating disease."

Four million Americans currently have Alzheimer's. Until recently, age and family history were the only well-established risk factors for Alzheimer's. But, for the first time, researchers may be on the verge of a better understanding of how people may be able to reduce the likelihood of developing the disease.

The Alzheimer's Association is hosting the 8th International Conference on Alzheimer's Disease and Related Disorders, July 20-25, 2002, in Stockholm, Sweden. The conference is the largest gathering of Alzheimer researchers in history. As many as 4,000 researchers from around the world will present and discuss the findings of nearly 2,000 studies on the prevention, diagnosis and treatment of Alzheimer's disease.

The Alzheimer's Association is the premier source of information and support for the millions of Americans with Alzheimer's. The largest private funder of Alzheimer research in the United States, the Association has committed $138 million toward research into the disease.

--- Abstract No. 503

Title: Chronic treatment with a functional gamma-secretase inhibitor reduces beta-amyloid burden and plaque pathology in PDAPP mice

Session: Sunday, July 21, 3-5 p.m.

Presenters: P.May, L. Altstiel, M. Bender, L. Boggs, D. Calligaro, K. Fuson, B. Gitter, P. St. George-Hyslop, W. Jordan, M. Kallman, W.Li, T. Mabry, R. Mark, B. Ni, J. Nissen, W. Porter, S. Sorgen, Y. Su, J. Audia, H. Dovey, D. Games, V. John, S. Freedman, T. Guido, K. Johnson-Wood, K. Khan, L. Latimer, I. Lieberburg, P. Seubert, E. Thorsett, F. Soriano, D. Schenk

--- Editor's Note: News releases of selected research presented at the 8th International Conference on Alzheimer's Disease and Related Disorders are available on the Alzheimer's Association's Web site, at www.alz.org/internationalconference/newsroom.htm. Scientific abstracts are accessible on the Web at http://www.alz.org/internationalconference/programs.htm, then click on Program Navigator link.