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Researchers close in on origins of main ingredient of Alzheimer's plaques
Date:4/9/2008

St. Louis, Aprl 8, 2008 The ability of brain cells to take in substances from their surface is essential to the production of a key ingredient in Alzheimer's brain plaques, neuroscientists at Washington University School of Medicine in St. Louis have learned.

The researchers used a drug to shut down the intake process, known as endocytosis, in a mouse model of Alzheimer's disease. The change led to a 70 percent drop in levels of amyloid beta, the protein fragment that clumps together to form Alzheimer's plaques. Importantly, they also found that endocytosis' ability to increase amyloid beta was coupled to normal nerve cell communication called synaptic activity.

"Blocking endocytosis isn't a viable option for treatment because cells throughout the body, including brain cells, need endocytosis for healthy function," says first author John Cirrito, Ph.D., research instructor in neurology. "But we are starting to understand the origins of amyloid beta in more detail now, and what were learning is opening other options we can pursue to seek new treatments for Alzheimer's disease."

While endocytosis is necessary for normal function of brain cells, Cirrito and others believe it may accidentally be causing the cells to take in the amyloid precursor protein (APP), which breaks down into amyloid beta. If so, a drug that reduces brain cells' intake of APP may help reduce amyloid beta production.

The results appear in the April 10 issue of Neuron.

Other research had shown previously that endocytosis might be important for amyloid beta production, and that amyloid beta is produced inside brain cells. In 2005, Cirrito and his colleagues linked increased communication between brain cells to higher amyloid beta levels.

Cirrito decided to test both endocytosis and brain cell activity in a coordinated fashion. He used a technique known as microdialysis that he had previously adapted for Alzheimer's research to monitor th
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Contact: Michael Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
Source:Eurekalert

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