Cholesterol modulates the formation of Aβ ion channel in lipid bilayers

The misfolding of amyloid beta (Aβ) is one of the predominant hallmarks in the pathology of Alzheimer’s disease (AD). In this study, we showed that the formation of Aβ ion channel on the membrane depended on cholesterol concentration. From a mechanical aspect, we found that cholesterol levels affected the stability and assembly of lipid bilayers. Measurements on planar lipid bilayers indicated that a small amount of cholesterol interacted with Aβ proteins and promoted the insertion process. Conversely, high cholesterol integrated the lipid bilayer and exerted an opposite effect on Aβ insertion. Aβ ion channel was then detected by graphene-based field-effect transistors. Results demonstrated that Aβ ion channel promoted Ca2+ flux in the presence of 15% cholesterol but prevent Ca2+ flux in high cholesterol. Thus, cholesterol had a complex impact on Aβ ion channel that can be described as two different effects. First, a small amount of cholesterol interacted with Aβ and facilitated Aβ ion-channel formation i...