Alzheimer's disease-related amyloid β peptide causes structural disordering of lipids and changes the electric properties of a floating bilayer lipid membrane.

Neurodegeneration in Alzheimer's disease is associated with disruption of the neuronal cell membrane by the amyloid β (Aβ) peptide. However, the disruption mechanism and the resulting changes in membrane properties remain to be elucidated. To address this issue, herein the interaction of amyloid β monomers (AβMs) and amyloid β oligomers (AβOs) with a floating bilayer lipid membrane (fBLM) was studied using electrochemical and IR spectroscopy techniques. IR measurements showed that both Aβ forms interacted similarly with the hydrophobic membrane core (lipid acyl chains), causing conformational and orientational changes of the lipid acyl chains, thus decreasing acyl chain mobility and altering the lipid packing unit cell. In the presence of AβOs, these changes were more significant than those in the presence of AβMs. However, respective interactions of AβMs and AβOs with the membrane hydrophilic exterior (lipid heads) were quite different. AβMs dehydrated lipid heads without affecting their orientation while AβOs changed the orientation of lipid heads keeping their hydration level intact. Electrochemical measurements showed that only AβOs porated the fBLM, thus significantly changing the fBLM electrical properties. The present results provide new molecular-level insight into the mechanism of membrane destruction by AβOs and changes in the membrane properties.