title: Characterization of high-affinity binding between gangliosides and amyloid beta-protein.
abstract: The binding specificities of amyloid beta-protein (A beta) such as A beta 1-40, A beta 1-42, A beta 40-1, A beta 1-38, A beta 25-35, and amyloid beta precursor protein (beta-APP) analogues for different glycosphingolipids were determined by surface plasmon resonance (SPR) using a liposome capture method. A beta 1-42, A beta 1-40, A beta 40-1, and A beta 1-38, 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 beta were found to have higher affinity to GM1 ganglioside than fresh or soluble derivatives. A beta 1-40 bound to a number of gangliosides with the following order of binding strength: GQ1b alpha > GT1a alpha > GQ1b > GT1b > GD3 > GD1a = GD1b > LM1 > GM1 > GM2 = GM3 > GM4. Neutral glycosphingolipids had a lower affinity for A beta 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 alpha2,3NeuAc residue on the neutral oligosaccharide core is required for binding. In addition, the alpha2-6NeuAc residue linked to GalNAc contributes significantly to binding affinity for A beta.
authors.affiliation: Tsukuba Research Laboratories, Eisai Co. Ltd, Ibaraki, Japan. t-ariga@hhc.eisai.co.jp
authors.forename: T
authors.initials: T
authors.lastname: Ariga
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: A
authors.initials: A
authors.lastname: Hasegawa
authors.forename: M
authors.initials: M
authors.lastname: Kiso
authors.forename: H
authors.initials: H
authors.lastname: Ishida
authors.forename: T
authors.initials: T
authors.lastname: Miyatake
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D005732:Gangliosides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance
chemical_list: D016229:Amyloid beta-Peptides; D005732:Gangliosides; D019158:N-Acetylneuraminic Acid