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Spectroscopy
Volume 17, Issue 2-3, Pages 241-254
http://dx.doi.org/10.1155/2003/185737

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

Tania Valdes-Gonzalez,1,2 Junichi Inagawa,3 and Tatsuo Ido1,2

1Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Aramaki, Aoba, Sendai 980‒8578, Japan
2Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki, Aoba, Sendai 980‒8578, Japan
3Biacore, Tokyo, Japan

Copyright © 2003 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Interactions between β‒amyloid (Aβ) 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 Aβ25‒35, Aβ40 and Aβ42 with surfaces containing single glycolipids (Asialo‒GM1, GM1, GD1a or GT1b). The larger peptides interacted with gangliosides stronger than Aβ25‒35, which showed some significant bindings solely at high concentrations under acidic conditions. Only the interactions at low Aβ 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 Aβ with the membranes containing gangliosides, due to the following process: when Aβ is injected at a critical concentration, the first molecules that interact with the gangliosides remain fixed on the membrane. Next Aβ molecules bind to these fixed molecules, so that for each Aβ 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 Aβ 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 Aβ deposition could simulate the initial stage of the Aβ peptide accumulation on cell surfaces.