Argonne research offers clues to Alzheimer's plaques

ARGONNE, Ill. (May 2, 2003) - Researchers from the U.S. Department of Energy's Argonne National Laboratory and the University of Chicago have developed methods to directly observe the structure and growth of microscopic filaments that form the characteristic plaques found in the brains of those with Alzheimer's Disease.

No one knows if these " -amyloid plaques" cause the disease, or are merely a symptom. But as America ages - people over 85 are the fastest-growing segment of the population, and 30 to 40 percent of them will contract the disease - every clue may help medical science slow or stop the coming epidemic.

"The three-dimensional structure of the entire -amyloid fibril is the largest noncrystalline structure ever characterized," said Argonne researcher P. Thiyagarajan, one of the project's principal investigators.

Previous research in the field had shown that each plaque is a tangle of millions of ribbon-like peptide chains called -amyloid fibrils. Peptides are chains of amino acids, simple organic compounds that form the building blocks of proteins. Inside the body's cells, amino acids are used for growth, maintenance and repair. Some peptides are needed for physiological processes; others have antibacterial properties.

Amyloid peptides are chains of 40 to 42 amino acid residues. Due to their unique chemical architecture, consisting of water-loving and water-avoiding amino acid sequences, Alzheimer's peptides "self-assemble" to form tangles of fibrils in the brains of persons with Alzheimer's Disease.

Alzheimer's peptides seem to associate laterally, stacking on top of the other to form ribbon-like structures - the beginnings of a fibril. The ribbon-like structures further associate to form thick twisting fibrils. Inside the brain, these fibrils can further associate and form insoluble plaques.

The insolubility of these large peptides prevented researchers from carrying out studies of their self-assembly.

Contact: Dave Jacque
DOE/Argonne National Laboratory

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