Copper modulation of amyloid beta 42 interactions with model membranes

Abstract

Growing evidence supports that interactions of the amyloid- peptide Aβ(142) with neuronal cell membranes and copper are involved in Alzheimer's disease pathogenesis. We report using solid-state NMR that the peptide significantly perturbed the phosphate and upper acyl chain region of bilayers comprising brain total lipid extract to cause domain segregation. Deep headgroup perturbations were also realized for palmitoyloleoylphospatidylcholinecholesterol model systems; however, incorporating 10% palmitoyloleoylphosphatidylserine or the ganglioside GM1 resulted in a more peripheral interaction. Cu 2+ at a 1:7 molar ratio to peptide caused deeper penetration into model systems, but partially atte..