 | Piecing Together the Alzheimer’s Puzzle
St. Louis, July 22, 2002 —A protein called clusterin may be an essential link in the molecular chain of events that leads to Alzheimer's disease, according to research led by Washington University School of Medicine in St. Louis. The study will appear online the week of July 22 in the Proceedings of the National Academy of Sciences.
A key step in the development of Alzheimer's disease is the formation of sticky plaques in the brain, composed primarily of clumps of insoluble amyloid beta (Aß) protein. Clusterin belongs to a family of proteins that can bind Aß and was believed to potentially play a role in the development of Alzheimer’s disease.
David M. Holtzman, M.D., the Charlotte and Paul Hagemann Professor of Neurology and associate professor of molecular biology and pharmacology, led the research. The first author of the study is Ronald DeMattos, Ph.D., former instructor in neurology. The Washington University team worked in collaboration with researchers at the Children's Hospital Research Foundation in Cincinnati, the University of Cincinnati and Eli Lilly and Company, where DeMattos now works.
The team compared two groups of genetically-engineered mice. The first group was a common mouse model of Alzheimer’s disease, with brain changes similar to those in humans with the disease. The second group had the same Alzheimer’s-like disorder, but also lacked clusterin.
Both groups of mice developed about the same amount of Aß accumulation. However, those lacking clusterin had fewer Aß fibrils, or threads, an important step in the development of toxic Aß plaques. They also had significantly less damage to brain cells surrounding the AB deposits, suggesting that clusterin makes Aß more toxic to surrounding cells.
According to Holtzman, “these findings suggest that clusterin is a potentially important piece of the Alzheimer's puzzle and a possible target for Alzheimer's therapies.”
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DeMattos RB, O’Dell MA, Parsadanian M, Taylor JW, Harmony JAK, Bales KR, Paul SM, Aronow BJ, Holtzman DM. Clusterin promotes amyloid plaque formation and is critical for neuritic toxicity in a mouse model of Alzheimer’s disease. Proceedings of the National Academy of Sciences, July 2002.
Funding from the National Institute on Aging supported this research.
The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons 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. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
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