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.