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Toxic protein could explain Alzheimer's and lead to breakthroughs

EVANSTON, Ill. -- Researchers at Northwestern University have discovered for the first time in humans the presence of a toxic protein that they believe to be responsible for the devastating memory loss found in individuals suffering from Alzheimer's disease.

An understanding of this key molecular link in the progression of Alzheimer's could lead to the development of new therapeutic drugs capable of reversing memory loss in patients who are treated early, in addition to preventing or delaying the disease. Help for individuals with pre-Alzheimer's memory failure (mild cognitive impairment) also is envisioned. The findings will be published online by the Proceedings of the National Academy of Sciences during the week of Aug. 18.

The research team, led by William L. Klein, professor of neurobiology and physiology, found up to 70 times more small, soluble aggregated proteins called "amyloid b-derived diffusible ligands" (ADDLs, pronounced "addles") in the brain tissue of individuals with Alzheimer's disease compared to that of normal individuals.

The clinical data strongly support a recent theory in which ADDLs accumulate at the beginning of Alzheimer's disease and block memory function by a process predicted to be reversible. ADDLs have the ability to attack the memory-building activity of synapses, points of communication where neurons exchange information, without killing neurons.

"Researchers for more than a decade thought it was big molecules, the 'amyloid fibrils,' that caused memory problems, but we think the real culprits are extremely small molecules, what we call ADDLs," said Klein, who is a member of Northwestern's Cognitive Neurology and Alzheimer's Disease Center. "Now we've shown that ADDLs are present in humans and are a clinically valid part of Alzheimer's pathology. If we can develop drugs that target and neutralize these neurotoxins, it might be possible to not only slow down memory loss, but to actually reverse it, t
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Contact: Megan Fellman
fellman@northwestern.edu
847-491-3115
Northwestern University
18-Aug-2003


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