A new structural model of Aβ 40 fibrils

Abstract

The amyloid fibrils of beta-amyloid (Aβ) peptides play important roles in the pathology of Alzheimer's disease. Comprehensive solid-state NMR (SSNMR) structural studies on uniformly isotope-labeled Aβ assemblies have been hampered for a long time by sample heterogeneity and low spectral resolution. In this work, SSNMR studies on well-ordered fibril samples of Aβ 40 with an additional N-terminal methionine provide high-resolution spectra which lead to an accurate structural model. The fibrils studied here carry distinct structural features compared to previous reports. The inter-β-strand contacts within the U-shaped β-strand-turn-β-strand motif are shifted, the N-terminal region adopts a β-conformation, and new inter-monomer contacts occur at the protofilament interface. The revealed structural diversity in Aβ fibrils points to a complex picture of Aβ fibrillation. © 2011 American Chemical Society.