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2006 Grant - Axelsen

The Structure of Neurotoxic Intermediate Forms of Beta-Amyloid Proteins

Paul H. Axelsen, M.D.
University of Pennsylvania
Philadelphia, Pennsylvania

2006 Zenith Fellows Award

Beta-amyloid protein fragments, key suspects in Alzheimer's disease pathology, assemble themselves into structures in a series of distinct steps. Some of the larger assemblies have been relatively well characterized in previous research. But the initial assemblies of just a few beta-amyloid fragments, or beta-amyloid oligomers, are difficult to study using the standard tools of biology that reveal the structures of small molecules. A better understanding of these oligomers is important, however, because a growing body of evidence points to these small assemblies as the primary toxic culprits in Alzheimer's disease.

Paul H. Axelsen, M.D., and colleagues propose to study the structural properties of beta-amyloid oligomers using a relatively new technique called two-dimensional infrared correlation spectroscopy. This technique has the potential to yield precise distances and relative orientations of structures within an oligomer. This work should enable them to characterize the structural properties of these early assemblies and may reveal how individual beta-amyloid fragments fit together.

The outcome of such work may provide valuable information to understand the toxic properties of beta-amyloid oligomers and to develop drugs that inhibit their assembly or break them down.