Structural analysis of amyloid aggregates by multifunctional fluorescence nanoscopy

Abstract

An oligomeric structure of amyloid β protein (Aβ) is one of the probable neurotoxic agent in Alzheimer's disease (AD). Multifunctional nanoscopy, which incorporates fluorescence correlation spectroscopy (FCS), atomic force microscopy (AFM) and fluorescence lifetime imaging microscopy (FLIM), was used to characterize these oligomeric Aβ structures. FCS data showed that various sizes of Aβ aggregates exist simultaneously in the solution phase, spanning from nm to μm scale. Stable oligomeric Aβ nanoparticles were prepared and their topological details of Aβ aggregates were investigated by AFM. Fluorescence lifetime imaging of Aβ oligomers stained with FRET (fluorescence resonance energy transfer) amyloids demonstrated that micelle and donut structures both exist in different pHs and temperatures. © 2006 Elsevier B.V. All rights reserved.