Amyloid β-peptide interaction with GM1 containing model membrane

Abstract Early impairments in Alzheimer’s disease are related to neuronal membrane damage. Aberrant Amyloid β (Aβ) species and specific membrane components both play a role in promoting aggregation, deposition and signal dysfunction. Ganglioside GM1, present with cholesterol and sphingomyelin in lipid rafts, seems to be able to interact with Aβ and initiate Aβ aggregation on membrane. In this chapter, several studies are reviewed, highlighting the role of different lipids and in particular GM1 in the interaction between Aβ and membrane systems. Results concerning GM1-Aβ interaction obtained by means of different experimental methods are reported and discussed. Small angle X-ray scattering is used to study the structure of the unilamellar vesicle bilayer. Mixing Aβ species with vesicles clearly showed an effect on the bilayer structure, but only for GM1-containing liposomes. The elastic properties of GM1-containing membrane have been studied by Neutron Spin Echo, showing that the presence of Aβ species brings about an increase in the membrane rigidity, as reflected by the measured elastic modulus. This effect can be hindered by the presence of molecular chaperones, like Hsp60. This chaperonin has proven to be a strong inhibitor of the amyloidogenesis process, due to its dose dependent ability to neutralize oligomeric metastable species needed to onset the fibril growth cascade. The fact that the incubation of Aβ in the presence of Hsp60 leads to a loss of the Aβ effects on the membrane dynamical properties suggests that the aberrant interaction between Aβ and membranes is important in these specific intermediate Aβ species.