Characterization of high-affinity binding between gangliosides and amyloidbeta-protein

The binding specificities of amyloid beta -protein (A B) such as A beta 1-4 0, A beta 1-42, A beta 40-1, A beta 1-38, A beta 25-35, and amyloid beta pr ecursor protein (beta -APP) analogues for different glycosphingolipids were determined by surface plasmon resonance (SPR) using a liposome capture met hod. A beta 1-42, A beta 1-40, A beta 40-1, and A beta 1-28, but not A beta 25-35, bound to GM1 ganglioside in the following rank order: A beta 1-42 > A beta 40-1 > A beta 1-40 > A beta 1-38. The beta -APP analogues bound to GM1 ganglioside with a relatively lower affinity. Aged derivatives of A bet a were found to have higher affinity to GM1 ganglioside than fresh or solub le derivatives, A beta 1-40 bound to a number of gangliosides with the foll owing order of binding strength: GQ1b alpha > GT1a alpha > GQ1b > GT1b > GD 3 > GD1a = GD1b > LM1 > GM1 > GM2 = GM3 > GM4. Neutral glycosphingolipids h ad a lower affinity for A beta 1-40 than gangliosides with the following or der of binding strength: Gb4 > asialo-GM1 (GA1) > Gb3 > asialo-GM2(GA2) = L acCer. The results seem to indicate that an alpha2,3NeuAc residue on the ne utral oligosaccharide core is required for binding. In addition, the alpha2 -6NeuAc residue linked to GalNAc contributes significantly to binding affin ity for A beta. (C) 2001 Academic Press.