Soluble multimeric Alzheimer beta(1-40) pre-amyloid complexes in dilute solution

Neurobiol Aging. 1995 Sep-Oct;16(5):755-64. doi: 10.1016/0197-4580(95)00052-g.

Abstract

Aqueous solutions of beta(1-40) peptide spontaneously associate to form pentameric/hexameric complexes that can be demonstrated by SDS-PAGE following treatment with glutaraldehyde and borohydride reduction. Under amyloidogenic conditions of pH and high peptide concentration these aggregates can further associate to form pentameric/hexameric complexes that can be demonstrated by SDS-PAGE following treatment with glutaraldehyde and borohydride reduction. Under amyloidogenic conditions of pH and high peptide concentration these aggregates can further associate to form sedimentable and filterable structures with beta-sheet amyloid characteristics of Thioflavine T fluorescence. The presence of such preamyloid structures at low peptide concentration suggests a mechanism by which amyloid plaques can accrete additional material by a cooperative rather than monomeric growth. The existence of a monomer<==>multimer equilibrium may partly explain the divergence of biological consequences with respect to neurotoxicity.

MeSH terms

  • Amino Acid Sequence
  • Amyloid beta-Peptides / analysis
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Protein Precursor / analysis
  • Amyloid beta-Protein Precursor / chemistry*
  • Amyloid beta-Protein Precursor / ultrastructure
  • Cross-Linking Reagents / pharmacology
  • Glutaral / pharmacology
  • Microscopy, Electron
  • Molecular Sequence Data
  • Peptide Fragments / analysis
  • Peptide Fragments / chemistry*
  • Polymers
  • Solubility
  • Solutions

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Cross-Linking Reagents
  • Peptide Fragments
  • Polymers
  • Solutions
  • amyloid beta-protein (1-40)
  • Glutaral