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

摘要

Amyloid β-peptide (Aβ) is a major component of plaques in Alzheimer's disease, and formation of senile plaques has been suggested to originate from regions of neuronal membrane rich in gangliosides. We analyzed the mode of interaction of Aβ with lipid bilayers by multinuclear NMR using 31 P nuclei. We found that Aβ (1-40) strongly perturbed the bilayer structure ofdimyristoylphosphatidylcholine (DMPC), to form a non-lamellar phase (most likely micellar). The ganglioside GM1 potentiated the effect of Aβ (1-40), as viewed from 31 P NMR. The difference of the isotropic peak intensity between DMPC/Aβ and DMPC/GM1 /Aβ suggests a specific interaction between Aβ and GM1. We show that in the DMPC/GM1 /Aβ 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 Aβ peptide, and facilitated by GM1.