Toxic protein could explain Alzheimer's and lead to bre...( o bring memory function back to normal....)

Although both are a form of amyloid beta, ADDLs and their properties differ significantly from the amyloid fibrils (known as plaques) that are a diagnostic hallmark of Alzheimer's. ADDLs found in human brains, mostly 12 or 24 amyloid beta proteins clumped together, are tiny and undetectable in conventional neuropathology; fibrils are much, much larger. While fibrils are immobile toxic waste dumps, ADDLs are soluble and diffuse between brain cells until they find vulnerable synapses. (Single pieces of amyloid beta protein in the brain is normal.)

"The difference between ADDLs and fibrils is like comparing four eggs, over easy, to an enormous omelet that could feed the entire Chicago Bears team," said Klein. ""You start with eggs, but the final product taste, texture and size are all different."

The existence of ADDLs may help explain the poor correlation between plaques and neurological deficits. Studies by other researchers have shown a reversal of memory failure in mouse models treated with amyloid beta antibodies -- but without any reduction in plaque. The antibodies appear to restore memory because they neutralize ADDLs, which Klein's group has found in mouse models with Alzheimer's as well as in human brains with Alzheimer's.

Klein's research team recently began a study funded by the National Institutes of Health to continue investigating ADDLs in humans and further characterize these molecules. In addition to Alzheimer's disease, ADDL-like molecules could be the cause of other degenerative diseases.

Klein also is working with researchers at Northwestern's Institute for Nanotechnology on clinical diagnostics capable of detecting ADDLs in blood or cerebral spinal fluid. Currently diagnosis of Alzheimer's is based primarily on a battery of psychological tests.

"Now that ADDLs have been discovered in humans we would like to develop effective diagnostics and that means empl
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Contact: Megan Fellman
fellman@northwestern.edu
847-491-3115
Northwestern University
18-Aug-2003