Molecular structure of a fibrillar Alzheimer's Aβ fragment

Amyloid-beta (A beta) peptide deposition as fibrillar senile plaques is a key element in the pathology of Alzheimer's disease. Here we present a high-resolution structure of an A beta amyloid fibril using magnetically aligned preparations of a central A beta domain which forms representative amyloid fibrils. Diffraction analysis of these samples revealed Bragg reflections on layer lines consistent with a preferred orientation, as opposed to the typical symmetry associated with fibers. These crystalline properties permitted a molecular replacement approach based upon a beta -hairpin motif resulting in a structure of the fibrillar A beta peptide. This detailed molecular structure of A beta in its fibrous state provides clues as to the mechanism of amyloid assembly and identifies potential targets for controlling the aggregation process.