Localization of amyloid beta (Aβ1-42) protofibrils in membrane lateral compartments: Effect of cholesterol and 7-Ketocholesterol

Cholesterol plays an important role in the interaction of Alzheimer's amyloid beta (A beta) with cell membranes, an important event in A beta-induced cytotoxicity. However, it is not fully understood how cholesterol influences the association of Ab with membrane lateral compartments. We have shown that by modulating membrane fluidity, cholesterol decreased peptide localization in solid-ordered domains and increased that in liquid-ordered domains. It changed the amount of A beta associating with liquid-disordered (Ld) phase with different tendencies depending on the composition of heterogeneous membrane systems. 7-Ketocholesterol, an oxidized derivative of cholesterol, majorly enhanced the fluidity of and A beta interaction with Ld phase. These findings are useful for clarifying the impact of cholesterol and its oxidation in A beta-induced toxicity. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.