Amyloid beta-peptide insertion in liposomes containing GM1-cholesterol domains

Neuronal membrane damage is related to the early impairments appearing in Alzheimer's disease due to the interaction of the amyloid ?-peptide (A?) with the phospholipid bilayer. In particular, the ganglioside GM1, present with cholesterol in lipid rafts, seems to be able to initiate A? aggregation on membrane. We studied the thermodynamic and structural effects of the presence of GM1 on the interaction between A? and liposomes, a good membrane model system. Isothermal Titration Calorimetry highlighted the importance of the presence of GM1 in recruiting monomeric A? toward the lipid bilayer. Light and Small Angle X-ray Scattering revealed a different pattern for GM1 containing liposomes, both before and after interaction with A?. The results suggest that the interaction with GM1 brings to insertion of A? in the bilayer, producing a structural perturbation down to the internal layers of the liposome, as demonstrated by the obtained electron density profiles.