Alzheimer's amyloid fibrils: structure and assembly

Biochim Biophys Acta. 2000 Jul 26;1502(1):16-30. doi: 10.1016/s0925-4439(00)00029-6.

Abstract

Structural studies of Alzheimer's amyloid fibrils have revealed information about the structure at different levels. The amyloid-beta peptide has been examined in various solvents and conditions and this has led to a model by which a conformational switching occurs from alpha-helix or random coil, to a beta-sheet structure. Amyloid fibril assembly proceeds by a nucleation dependent pathway leading to elongation of the fibrils. Along this pathway small oligomeric intermediates and short fibrillar structures (protofibrils) have been observed. In cross-section the fibril appears to be composed of several subfibrils or protofilaments. Each of these protofilaments is composed of beta-sheet structure in which hydrogen bonding occurs along the length of the fibre and the beta-strands run perpendicular to the fibre axis. This hierarchy of structure is discussed in this review.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / ultrastructure
  • Animals
  • Congo Red
  • Humans
  • Microscopy, Atomic Force
  • Molecular Structure
  • Neurons / pathology
  • Peptide Fragments / chemistry
  • Plaque, Amyloid / chemistry
  • Protein Conformation*
  • Protein Structure, Secondary
  • Solubility
  • X-Ray Diffraction

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (11-25)
  • Congo Red