Cholesterol in cell membrane plays an important role in the pathogenesis of Alzheimer's disease, but the exact function of cholesterol in the regulation of A� generation, aggregation, and toxicity remains elusive. Here, we investigate the effect of cholesterol contents on adsorption behaviors, insertion/exit pathways, and dynamical structures of A�1-42 monomers and dimers in the POPC bilayers containing 0%, 20%, and 40% cholesterol. MD simulations show that cholesterol increases bilayer thickness, hydrophobic chain order, and surface hydrophobicity, and decreases phospholipid mobility. All these effects promote the association of A� with the POPC bilayer. A� dimer appears to more preferentially stay in the POPC bilayer than A� monomer presumably due to enhanced peptide-peptide interactions. Moreover, hydrophobic C-terminal residues show strong tendency to interact with or insert into the bilayer. This work supports that cholesterol in cell membrane acts as a promoter for A�-membrane interactions, which facilitate A� aggregation and membrane insertion.

Cholesterol promotes the interaction of amyloid-ß peptides with lipid bilayer

243rd National Meeting (2012)

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