Interplay Between Amyloid Beta-Peptide and Cholesterol in Bilayer

Abstract

The interaction between lipid bilayers and amyloid beta-peptide (Aβ) is of great interest in understanding Alzheimer's disease (AD). Accumulating evidence points to a positive association of cholesterol in the membrane and AD, but a molecular-level interaction between cholesterol and Aβ has not been established. As an essential part of the membrane, cholesterol enhances the fluidity of the lipid bilayer, which may reduce membrane permeation caused by Aβ, potentially alleviating its ability to rupture the membrane. On the other hand, cholesterol increases the binding affinity of Aβ to model lipid membranes, as Aβ shows little affinity to cholesterol-free membranes. We studied the Aβ conformations change in a model lipid membrane of DMPC/DMPG/cholesterol by circular dichroism, isothermal titration calorimetry and fluorescence. The structural changes in lipid bilayers caused by Aβ was studied by grazing angle neutron diffraction (GAND) on multilamellar lipid membrane samples in conjunction with solution Small-Angle Neutron Scattering (SANS) on lipid vesicles. The experiments combine to provide new molecular level details about how cholesterol and Aβ interact in the lipid membrane.