CHICAGO --- Researchers have discovered new, highly toxic proteins that disrupt brain mechanisms for learning and memory and which may set off the progression of Alzheimer's disease.

The globular-shaped proteins, called amyloid beta-derived diffusible ligands (or ADDLs), were identified by a team of neuroscientists at Northwestern University, Evanston Northwestern Healthcare and the University of Southern California, Los Angeles.

A report on the group's findings appears in the May 26 issue of the Proceedings of the National Academy of Sciences.

ADDLs are a surprising new form of the amyloid beta protein. Amyloid beta has been known for years to accumulate as enormous fibers in Alzheimer's afflicted brains. A long-standing hypothesis has been that these fibers attack nerve cells and cause Alzheimer's dementia. These scientists now have found that ADDLs, which are minuscule clumps of amyloid beta only a tiny fraction the size of a fiber, may be more relevant to the disease process.

Their experiments in laboratory specimens found that, even at highly dilute concentrations, ADDLs interfere with long-term potentiation, one of the nerve cell processes that is essential to learning and memory. This dysfunction occurred well in advance of the cellular degeneration considered by many researchers to be the cause of Alzheimer's disease. Cell death, when it did occur, was most evident in the hippocampus, the brain's "storage bin" for short-term memory, said William L. Klein, senior author on this study. Klein is a professor of neurobiology and physiology and of neurology at Northwestern.

"Our work suggests that corruption of such signaling by ADDLs may account for the loss of synaptic memory formation at the early stages of Alzheimer's disease and for the nerve cell death and profound dementia at end stages of the disease," he said.

ADDLs apparently form when certain inflammatory proteins are present
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Contact: Elizabeth Crown
e-crown@nwu.edu
312-503-8928
Northwestern University
25-May-1998