Tip‐Enhanced Raman Spectroscopy to Distinguish Toxic Oligomers from Aβ_{1<b>–</b>42} Fibrils at the Nanometer Scale

Abstract

Abstract For the first time, natural Aβ 1–42 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.