Multiple quantum solid-state NMR indicates a parallel, not antiparallel, organization of β-sheets in Alzheimer's β-amyloid fibrils

Senile plaques associated with Alzheimer's disease contain deposits of fibrils formed by 39- to 43-residue beta -amyloid peptides with possible neurotoxic effects. X-ray diffraction measurements on oriented fibril bundles have indicated an extended beta -sheet structure for Alzheimer's beta -amyloid fibrils and other amyloid fibrils, but the supramolecular organization of the beta -sheets and other structural details are not well established because of the intrinsically noncrystalline, insoluble nature of amyloid fibrils, Here we report solid-state NMR measurements, using a multiple quantum (MQ)C-13 NMR technique, that probe the beta -sheet organization in fibrils formed by the full-length, 40-residue beta -amyloid peptide (A beta (1-40)) Although an antiparallel beta -sheet organization often is assumed and is invoked in recent structural models for full-length beta -amyloid fibrils, the MQNMR data indicate an in-register, parallel organization. This work provides site-specific, atomic-level structural constraints on full-length beta -amyloid fibrils and applies MQNMR to a significant problem in structural biology.