Beta-Amyloid Oligomer Formation in Physiological Solutions - a Study by Single-Molecule Fluorescence Resonance Energy Transfer

Abstract

Formation of oligomers of β-amyloid (Aβ) peptides is a pivotal initial event associated with the pathogenicity of Alzheimer's disease (AD). Using the single-molecule fluorescence resonance energy transfer (FRET) microscopy technique, we have detected the very beginning of the formation of Aβ peptide oligomers in physiological solutions. The existence of oligomers is identified from the FRET between dyes individually bonded to the N-terminus of the 40-unit peptides. Several dimers and oligomers identified by the varying FRET efficiency have been detected. The dimer with the highest stability is characterized to have a distance of 43 A between its two N-termini, in an anti-parallel structure that is similar to that of the dimer unit (anti-parallel hairpin) that has been previously identified in the fibrils.