Characterization of the interactions of β-amyloid peptides with glycolipid receptors by surface plasmon resonance

Interactions between beta-amyloid (Abeta) peptides and neuronal membranes play an important role in Alzheimer's disease (AD). Using surface plasmon resonance we assayed a kinetic model to study the interactions of Abeta25-35, Abeta40 and Abeta42 with surfaces containing single glycolipids (Asialo-GM1, GM1, GD1a or GT1b). The larger peptides interacted with gangliosides stronger than Abeta25-35, which showed some significant bindings solely at high concentrations under acidic conditions. Only the interactions at low Abeta concentrations were useful to calculate the kinetic constants. The affinities increased at low pH. The specificity, but not the affinity correlated with the number of sialic acids in the ganglioside sugar moiety. The most important finding in this study, was a special group of sensorgrams with linear association phases that appeared for the interactions of Abeta with the membranes containing gangliosides, due to the following process: when Abeta is injected at a critical concentration, the first molecules that interact with the gangliosides remain fixed on the membrane. Next Abeta molecules bind to these fixed molecules, so that for each Abeta molecule bound, new binding sites are activated on the surface in a linear ratio, which explains the linear shape of the sensorgrams. This way a laminar-arranged Abeta accumulate is progressively formed on the membrane surface and fixed there. These linear sensorgrams were not observe with asialo-GM1 or DMPC, which indicates the main role of sialic acid in these interactions. This model for progressive Abeta deposition could simulate the initial stage of the Abeta peptide accumulation on cell surfaces.