Cholesterol Modulates the Formation of the 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 the Aβ ion channel on the membrane depended on the 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. The Aβ ion channel was then detected by graphene-based field-effect transistors. Results demonstrated that the Aβ ion channel promoted a Ca²⁺ flux in the presence of 15% cholesterol but prevented a Ca²⁺ flux in high cholesterol. Thus, cholesterol had a complex impact on the Aβ ion channel that can be described as two different effects. First, a small amount of cholesterol interacted with Aβ and facilitated the Aβ ion channel formation in the membrane. Second, a large amount of cholesterol did not induce the ion flux in the membrane, which can be explained by the cholesterol damage to the regular distribution of the lipid bilayer. Overall, this study suggested a possible approach to consider cholesterol levels for the treatment of AD patients.