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Interviewee: Bill Klein, Northwestern University
"Type 3" Diabetes?
Neuroscientist Bill Klein and colleagues at Northwestern University had previously discovered evidence that Alzheimer’s disease might actually be a form of diabetes of the brain. Prior studies by other researchers found that patients with Alzheimer’s disease had lower levels of insulin, and that their brains were insulin-resistant. Klein discovered that, in addition to the plaques and tangles in brains of those with Alzheimer’s, there were toxic proteins called ADDLs (pronounced "ADD-els").
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In normal brains, insulin binds to sites on cells called receptors, triggering a series of events that allow memories to form. By studying rat brain cell cultures in the lab, Klein’s team discovered how ADDLs can interfere with the memory-formation process. When they added the ADDLs, they attached to their own receptors on the cell surface and caused the insulin receptors to disappear.
“Insulin in the brain is just not working,” explains Klein. Even though it’s there, it doesn’t have a place to park. Its receptors seem to be less responsive to the insulin. That’s the same thing that occurs in type 2 diabetes outside of the brain."
In the current study, Klein and his colleagues at the Federal University of Rio de Janeiro, Brazil, tried a strategy to protect the insulin receptors from damage. Before adding ADDLs, they flooded the brain cells with a high concentration of insulin. The insulin treatment blocked the ADDLs from attaching to the ADDL receptors and completely protected the insulin receptors.
“In brains, it is indeed a battle between which signaling pathway is the stronger… Insulin for the force, and ADDLs for the dark side,” Klein adds.
But the injected insulin used by many diabetics does not reach the brain, so Klein says specific drugs will need to be developed that selectively target the brain. He points out that such drugs would also avoid affecting insulin function in the body. Klein’s team will soon study these strategies in a mouse model of Alzheimer’s. But Klein says that he is also trying to find vaccines that target ADDLs and that his goal is to combine vaccines with ways to enhance insulin function.
PUBLICATION: The Proceedings of the National Academy of Sciences, February 2, 2009
AUTHORS: Fernanda De Felice, Marcelo Vieira, Theresa Bomfim, Helena Decker, Pauline Velasco, Mary P. Lambert, Kirsten L. Viola, Wei-Qin Zhao, Sergio Ferreira, and William Klein
RESEARCH FUNDED BY: American Health Assistance Foundation, Alzheimer’s Association, National Institutes of Health-National Institute on Aging; Howard Hughes Medical Institute, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/Brazil, and Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro and Human Frontier Science Program.
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