Interaction between Alzheimer's amyloid-beta and amyloid-beta-metal complexes with cell membranes.

A number of observations indicate that the primary target of amyloid-beta (Abeta) peptide is the cellular membrane of neurons. In the context of these observations we investigated, using X-ray diffraction techniques, whether Abeta-metal complexes were able to affect lipid bilayers as a model of cell membranes. The binding of Al to Abeta 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 Abeta 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 Abeta-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 Abeta-Al complex. Our findings imply that Al, compared to the other Abeta-metal complexes tested, could have a specifically relevant effect in enhancing Abeta toxicity.