Amyloid-β peptide disruption of lipid membranes and the effect of metal ions

beta-Amyloid peptide (A beta), which is cleaved from the larger trans-membrane amyloid precursor protein, is found deposited in the brain of patients suffering from Alzheimer's disease and is linked with neurotoxicity. We report the results of studies of A beta(1-42) and the effect of metal ions (Cu2+ and Zn2+) on model membranes Using P-31 and H-2 solid-state NMR, fluorescence and Langmuir Blodgett monolayer methods. Both the peptide and metal ions interact with the phospholipid headgrOUPS and the effects on the lipid bilayer and the peptide structure were different for membrane incorporated or associated peptides. Copper ions alone destabilise the lipid bilayer and induced formation of smaller vesicles but when A beta(1-42) was associated with the bilayer membrane copper did not have this effect. Circular dichroism spectroscopy indicated that A beta(1-42) adopted more beta-sheet structure when incorporated in a lipid bilayer in comparison to the associated peptide, which was largely unstructured. Incorporated peptides appear to disrupt the membrane more severely than associated peptides, which may have implications for the role of A in disease states. (c) 2005 Elsevier Ltd. All rights reserved.