Molecular structure of a fibrillar Alzheimer's A beta fragment

Amyloid-beta (Abeta) 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 Abeta amyloid fibril using magnetically aligned preparations of a central Abeta 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 Abeta peptide. This detailed molecular structure of Abeta in its fibrous state provides clues as to the mechanism of amyloid assembly and identifies potential targets for controlling the aggregation process.