Amyloid-β oligomers have a profound detergent-like effect on lipid membrane bilayers, imaged by atomic force and electron microscopy

The ability of amyloid- peptide (A) to disrupt membrane integrity and cellular homeostasis is believed to be central to Alzheimer's disease pathology. A is reported to have various impacts on the lipid bilayer, but a clearer picture of A influence on membranes is required. Here, we use atomic force and transmission electron microscopies to image the impact of different isolated A assembly types on lipid bilayers. We show that only oligomeric A can profoundly disrupt the bilayer, visualized as widespread lipid extraction and subsequent deposition, which can be likened to an effect expected from the action of a detergent. We further show that A oligomers cause widespread curvature and discontinuities within lipid vesicle membranes. In contrast, this detergent-like effect was not observed for A monomers and fibers, although A fibers did laterally associate and embed into the upper leaflet of the bilayer. The marked impact of A oligomers on membrane integrity identified here reveals a mechanism by which these oligomers may be cytotoxic.