Tip-Enhanced Raman Spectroscopy to Distinguish Toxic Oligomers from Aβ1-42 Fibrils at the Nanometer Scale

Angew Chem Int Ed Engl. 2017 Feb 6;56(7):1771-1774. doi: 10.1002/anie.201610399. Epub 2017 Jan 10.

Abstract

For the first time, natural Aβ1-42 fibrils (WT) implicated in Alzheimer's disease, as well as two synthetic mutants forming less toxic amyloid fibrils (L34T) and highly toxic oligomers (oG37C), are chemically characterized at the scale of a single structure using tip-enhanced Raman spectroscopy (TERS). While the proportion of TERS features associated with amino acid residues is similar for the three peptides, a careful examination of amide I and amide III bands allows us to clearly distinguish WT and L34T fibers organized in parallel β-sheets from the small and more toxic oG37C oligomers organized in anti-parallel β-sheets.

Keywords: amide bands; amyloid fibrils; oligomers; tip-enhanced Raman spectroscopy; toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics
  • Amyloid / chemistry*
  • Amyloid / genetics
  • Amyloid / ultrastructure
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / ultrastructure
  • Humans
  • Microscopy, Atomic Force / methods
  • Mutation
  • Peptide Fragments / chemistry*
  • Peptide Fragments / genetics
  • Peptide Fragments / ultrastructure
  • Spectrum Analysis, Raman / methods*

Substances

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