Structural conversion of neurotoxic amyloid-beta(1-42) oligomers to fibrils

Nat Struct Mol Biol. 2010 May;17(5):561-7. doi: 10.1038/nsmb.1799. Epub 2010 Apr 11.


The amyloid-beta(1-42) (Abeta42) peptide rapidly aggregates to form oligomers, protofibils and fibrils en route to the deposition of amyloid plaques associated with Alzheimer's disease. We show that low-temperature and low-salt conditions can stabilize disc-shaped oligomers (pentamers) that are substantially more toxic to mouse cortical neurons than protofibrils and fibrils. We find that these neurotoxic oligomers do not have the beta-sheet structure characteristic of fibrils. Rather, the oligomers are composed of loosely aggregated strands whose C termini are protected from solvent exchange and which have a turn conformation, placing Phe19 in contact with Leu34. On the basis of NMR spectroscopy, we show that the structural conversion of Abeta42 oligomers to fibrils involves the association of these loosely aggregated strands into beta-sheets whose individual beta-strands polymerize in a parallel, in-register orientation and are staggered at an intermonomer contact between Gln15 and Gly37.

Publication types

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

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amino Acid Sequence
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Cell Survival
  • Cells, Cultured
  • Cold Temperature
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Neurons / cytology*
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptide Fragments / chemistry*
  • Peptide Fragments / metabolism*
  • Protein Multimerization
  • Protein Structure, Secondary
  • Salts / chemistry


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