Characterization of High-Affinity Binding between Gangliosides and Amyloid β-Protein

The binding specificities of amyloid β-protein (Aβ) such as Aβ 1–40, Aβ 1–42, Aβ 40–1, Aβ 1–38, Aβ 25–35, and amyloid β precursor protein (β-APP) analogues for different glycosphingolipids were determined by surface plasmon resonance (SPR) using a liposome capture method. Aβ 1–42, Aβ 1–40, Aβ 40–1, and Aβ 1–38, but not Aβ 25–35, bound to GM1 ganglioside in the following rank order: Aβ 1–42 > Aβ 40–1 > Aβ 1–40 > Aβ 1–38. The β-APP analogues bound to GM1 ganglioside with a relatively lower affinity. Aged derivatives of Aβ were found to have higher affinity to GM1 ganglioside than fresh or soluble derivatives. Aβ 1–40 bound to a number of gangliosides with the following order of binding strength: GQ1b α > GT1a α > GQ1b > GT1b > GD3 > GD1a = GD1b > LM1 > GM1 > GM2 = GM3 > GM4. Neutral glycosphingolipids had a lower affinity for Aβ 1–40 than gangliosides with the following order of binding strength: Gb4 > asialo-GM1 (GA1) > Gb3 > asialo-GM2(GA2) = LacCer. The results seem to indicate that an α2,3NeuAc residue on the neutral oligosaccharide core is required for binding. In addition, the α2-6NeuAc residue linked to GalNAc contributes significantly to binding affinity for Aβ.