The interaction of amyloid A beta(1-40) with lipid bilayers and ganglioside as studied by P-31 solid-state NMR

摘要

Amyloid P-peptide (A beta) is a major component of plaques in Alzheimer's disease, and formation of senile plaques has been suggested to originate fro m regions of neuronal membrane rich in gangliosides. We analyzed the mode of interaction of A beta with lipid bilayers by multinuclear NMR using P-31 nuclei. We found that A beta (1-40) strongly perturbed the bilayer structure of dimyristoylphosphatidylcholine (DMPQ, to form a non-lamellar phase (most likely micellar). The ganglioside GM1 potentiated the effect of A beta (1-40), as viewed from P-31 NMR. The difference of the isotropic peak intensity between DMPC/A beta and DMPC/GM1/A beta suggests a specific interaction between A beta and GM1. We show that in the DMPC/GM1/A beta system there are three lipid phases, namely a lamellar phase, a hexagonal phase and non-oriented lipids. The latter two phases are induced by the presence of the A beta peptide, and facilitated by GM1. 9) 2008 Elsevier Ireland Ltd. All rights reserved.