Cholesterol is an important factor affecting the membrane insertion of beta-amyloid peptide (A beta 1-40), which may potentially inhibit the fibril formation.

beta-Amyloid peptide (A beta), 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 A beta and neuronal membranes have been postulated to play an important role in the neuropathology of Alzheimer's disease. Here we show that A beta is able to insert into lipid bilayer. The membrane insertion ability of A beta is critically controlled by the ratio of cholesterol to phospholipids. In a low concentration of cholesterol A beta 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%, A beta can insert spontaneously into lipid bilayer by its C terminus. During membrane insertion A beta 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 A beta prevents itself from aggregation and fibril formation by membrane insertion.