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

e results. In addition to allowing repeated sampling of the amyloid beta levels in the brains of live mice, the approach allows him to introduce drugs that reduce endocytosis and alter communication between brain cells.

When researchers gave mice the drug that stopped endocytosis, amyloid beta levels dropped by 70 percent. To see how much normal brain activity contributed to ongoing amyloid beta production in the absence of endocytosis, they then added a second drug that reduced brain cell communication. Amyloid beta levels did not decrease further.

When they reversed the experiment, reducing brain cell communication first, amyloid beta decreased by 60 percent. Adding the drug that stops endocytosis caused an additional small reduction in amyloid beta.

The results show that amyloid beta production requires both brain cell communication and endocytosis, but endocytosis is essential for a slightly larger share of amyloid beta. Basic nerve cell physiology may explain why.

The study focused on synapses, the region where nerve cells transmit messages by releasing chemicals from small compartments near the cell surface. To replenish those compartments, the nerve cell regularly takes them back in through endocytosis. The more active a brain cell is, the more often it has to bring these compartments back into the cell and refill them.

"Endocytosis can be messy in that it brings lots of substances into the cell from the membrane it internalizes," Cirrito says. "I think APP may be an innocent bystander in this process -- it just happens to be present on the cell surface when nerve cell communication causes more endocytosis. If there is a functional reason APP has to participate in this process, no one has found it."

Activity isn't the only cause of endocytosis in brain cells. The cells have other reasons for bringing in materials through endocytosis, and this additional intake could account for the small share of amyloid
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Contact: Michael Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
Source:Eurekalert

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