These beta amyloid "oligomers" can grow into insoluble "fibrils" that cluster around brain cells and are a hallmark of Alzheimer's disease. While monomers are produced from birth and appear to be relatively benign, oligomers have been implicated as potent toxins responsible for Alzheimer's-linked memory loss and brain cell death. This has led many scientists to speculate that oligomers may be the main culprit in Alzheimer's and therefore a prime target for a new generation of disease-modifying treatments.
To further confirm that these natural antibodies bind with oligomers, Dr. Relkin and his colleagues collaborated with Drs. Charles Glabe and Rakez Kayed from the University of California at Irvine, who had previously created anti-oligomer antibodies in rabbits. Using techniques pioneered by Dr. Glabe's group, the NewYork-Presbyterian/Weill Cornell scientists were able to measure and extract the human version of anti-oligomer antibodies from IVIG and then demonstrate that these antibodies are present in the blood of normal individuals.
The basis for the selective recognition of oligomers by these antibodies appears to be their capacity to recognize the oligomer's misfolded shape.
"That was a surprise, because most antibodies work by recognizing some aspect of the chemical structure of their target -- not their shape," explains Weill Cornell Medical College molecular biologist and study co-author, Dr. Paul Szabo. "That means that even though beta amyloid monomers and oligomers have the same fundamental chemical makeup, human anti-oligomer antibodies can distinguish between them. The antibodies recognize a particular shape that proteins assume only when they become these toxic aggregates."
The ability of the antibodies to recognize toxic proteins based on their shape may have important i
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Source:New York- Presbyterian Hospital/Columbia University Medical Center