AMYLOID DEPOSITION ALZHEIMER'S DISEASE

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Amyloid deposition in the brain is considered to be a marker for Alzheimer's disease, although a causal relationship has not been proven. The amyloid protein has not been available for study due to practical problems with its purification. In addition, current biophysical methods are not suited for the characterization of insoluble, noncrystalline proteins such as the amyloid proteins. Our work has focussed on these two problems. We have been successful in developing a synthetic route to the 0 protein which is amenable to scale-up. A novel biophysical approach (solid-state NMR and FTIR) has allowed us to observe details in amyloid structure which have heretofore escaped detection. We propose to continue the development of this approach. Our goal is to fully determine the molecular structure of the protein amyloid. We also are interested in using this structural information to design molecules which bind to amyloid (analogs of Congo red) and/or inhibit amyloid formation (conformationally-restrained peptide analogs). Finally, we hope to determine the sequence requirements for amyloid formation by comparing sequences from various amyloid-forming proteins.