Comparison of Alzheimer Abeta(1-40) and Abeta(1-42) amyloid fibrils reveals similar protofilament structures

Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):19813-8. doi: 10.1073/pnas.0905007106. Epub 2009 Oct 20.

Abstract

We performed mass-per-length (MPL) measurements and electron cryomicroscopy (cryo-EM) with 3D reconstruction on an Abeta(1-42) amyloid fibril morphology formed under physiological pH conditions. The data show that the examined Abeta(1-42) fibril morphology has only one protofilament, although two protofilaments were observed with a previously studied Abeta(1-40) fibril. The latter fibril was resolved at 8 A resolution showing pairs of beta-sheets at the cores of the two protofilaments making up a fibril. Detailed comparison of the Abeta(1-42) and Abeta(1-40) fibril structures reveals that they share an axial twofold symmetry and a similar protofilament structure. Furthermore, the MPL data indicate that the protofilaments of the examined Abeta(1-40) and Abeta(1-42) fibrils have the same number of Abeta molecules per cross-beta repeat. Based on this data and the previously studied Abeta(1-40) fibril structure, we describe a model for the arrangement of peptides within the Abeta(1-42) fibril.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / pathology*
  • Amyloid / chemistry
  • Amyloid / ultrastructure*
  • Amyloid beta-Peptides / chemistry*
  • Cryoelectron Microscopy
  • Hydrogen-Ion Concentration
  • Image Processing, Computer-Assisted
  • Microscopy, Electron, Transmission / methods
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Fragments / chemistry*
  • Protein Structure, Tertiary*
  • Spectroscopy, Fourier Transform Infrared / methods

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)