Cholesterol is an important factor affecting the membrane insertion of β-amyloid peptide (Aβ1-40), which may potentially inhibit the fibril formation

beta-Amyloid peptide (Abeta), a normal constituent of neuronal and non-neuronal cells, has been proven to be the major component of extracellular plaque of Alzheimer's disease. Interactions between Abeta and neuronal membranes have been postulated to play an important role in the neuropathology of Alzheimer's disease. Here we show that Abeta is able to insert into lipid bilayer. The membrane insertion ability of Abeta is critically controlled by the ratio of cholesterol to phospholipids. In a low concentration of cholesterol Abeta prefers to stay in membrane surface region mainly in a beta-sheet structure. In contrast, as the ratio of cholesterol to phospholipids rises above 30 mol%, Abeta can insert spontaneously into lipid bilayer by its C terminus. During membrane insertion Abeta generates about 60% alpha-helix and removes almost all beta-sheet structure. Fibril formation experiments show that such membrane insertion can reduce fibril formation. Our findings reveal a possible pathway by which Abeta prevents itself from aggregation and fibril formation by membrane insertion.