Interaction between Alzheimer's Amyloid-β and Amyloid-β-Metal Complexes with Cell Membranes

Abstract

A number of observations indicate that the primary target of amyloid-β (Aβ) peptide is the cellular membrane of neurons. In the context of these observations we investigated, using X-ray diffraction techniques, whether Aβ-metal complexes were able to affect lipid bilayers as a model of cell membranes. The binding of Al to Aβ gave particular conformational properties to the peptide that led to a marked alteration of the lipid bilayer representing phospholipids located in the outer monolayer of cell membranes. This effect was peculiar, since in our experimental conditions Aβ alone did not affect the lipid architecture, whereas the Al salt did, but only at concentrations several orders of magnitude higher than those of the Aβ-Al complex. In accordance with the effects observed with lipid bilayers, studies with human neuroblastoma cells demonstrated an impairment of cell functioning only in the presence of Aβ-Al complex. Our findings imply that Al, compared to the other Aβ-metal complexes tested, could have a specifically relevant effect in enhancing Aβ toxicity.