ALUMINIUM INCREASES TOXIC EFFECTS OF AMYLOID BETA-PEPTIDES ON THE HUMAN ERYTROCYTE MEMBRANE AND MOLECULAR MODELS

Abstract

The amyloid ?-peptide (A?) and aluminum have been found, among other components, in the senile plaques from Alzheimer’s disease patients. Aggregated A? and aluminum are toxic to neurons but the mechanism of accumulation and toxicity remains poorly understood. It has been proposed that A? and aluminum toxicity results from A?– and aluminum–membrane interactions. For this reason it was thought of interest to study the effect that A? and aluminum could have on cell membranes. With this aim, A?(1–40), A?(1–42), and Al(III) were incubated with intact human erythrocytes, isolated unsealed human erythrocyte membranes (IUM), and molecular models of the erythrocyte membrane. These consisted in bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), phospholipids classes located in the outer and inner monolayers of the erythrocyte membrane, respectively. Their capacity to perturb the bilayer structures of DMPC and DMPE was assessed by X-ray diffraction, IUM were studied by fluorescence spectroscopy, and intact human erythrocytes were observed by scanning electron microscopy (SEM). It was found that A?(1–40) and A?(1–42) in the presence of Al(III) altered the erythrocyte morphology, in IUM induced an ordering effect at the bilayer hydrophobic region, and the structure of DMPC bilayers was perturbed, effects that were different and stronger of those induced by each A? and Al(III) separately.