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Mechanism of Alzheimer's suggests combination therapy needed
Date:3/17/2009

Researchers at the University of Illinois at Chicago College of Medicine have discovered a mode of action for mysterious but diagnostic protein snarls found in the brains of Alzheimer's patients that suggests a one-two punch of therapy may be needed to combat the neurodegenerative disease.

Alzheimer's disease, which may affect as many as 5 million Americans and is among the most costly diseases to society in the United States and Europe, is characterized by two distinctive protein malformations: amyloid plaques and tau tangles. Amyloid plaques are sticky deposits made up of a short protein called amyloid beta, and tau tangles are made of short filaments of the tau protein.

So far no one has been able to explain how amyloid beta and the tau tangles wreak their damage on the nervous system.

"We have known for a long time that amyloid beta was bad," said Scott Brady, professor and head of anatomy and cell biology at the UIC College of Medicine. "What we haven't understood is why it's bad."

The findings, reported in a new study appearing in the Proceedings of the National Academy of Sciences Online Early Edition for March 16-20, suggest promising new targets for combination therapy.

In previous work, published earlier this year, the researchers suggested how tau tangles work together with amyloid beta to create a perfect storm that destroys neural function and memory.

"Cell death occurs at a very late stage of the disease," said Brady, principal investigator of the study. "Long before the cells die they lose function, and that function is critical for the symptoms that we see."

Brady and his colleagues found that when short assemblies of amyloid -- rather than the long-chain plaques -- get inside neurons, they interfere with the cells' transport system. This limits their ability to send vital proteins and vesicles to where they are needed within the cell and interferes with the synaptic connec
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Contact: Jeanne Galatzer-Levy
jgala@uic.edu
312-996-1583
University of Illinois at Chicago
Source:Eurekalert

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