Atomic-Resolution Three-Dimensional Structure of Amyloid β Fibrils Bearing the Osaka Mutation

Despite its central importance for understanding the molecular basis of Alzheimer's disease (AD), high-resolution structural information on amyloid -peptide (A) fibrils, which are intimately linked with AD, is scarce. We report an atomic-resolution fibril structure of the A1-40 peptide with the Osaka mutation (E22), associated with early-onset AD. The structure, which differs substantially from all previously proposed models, is based on a large number of unambiguous intra- and intermolecular solid-state NMR distance restraints.