title: Uptake of raft components into amyloid β-peptide aggregates and membrane damage.
abstract: Amyloid aggregation and deposition of amyloid β-peptide (Aβ) are pathologic characteristics of Alzheimer's disease (AD). Recent reports have shown that the association of Aβ with membranes containing ganglioside GM1 (GM1) plays a pivotal role in amyloid deposition and the pathogenesis of AD. However, the molecular interactions responsible for membrane damage associated with Aβ deposition are not fully understood. In this study, we microscopically observed amyloid aggregation of Aβ in the presence of lipid vesicles and on a substrate-supported planar membrane containing raft components and GM1. The experimental system enabled us to observe lipid-associated aggregation of Aβ, uptake of the raft components into Aβ aggregates, and relevant membrane damage. The results indicate that uptake of raft components from the membrane into Aβ deposits induces macroscopic heterogeneity of the membrane structure.
authors.affiliation: Department of Microbiology and Infectious Diseases, Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan. Electronic address: sasahara@med.kobe-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sasahara
authors.affiliation: Research Center for Environmental Genomics, Kobe University, Kobe 657-8501, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Morigaki
authors.affiliation: Department of Microbiology and Infectious Diseases, Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Mori
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000682:Amyloid / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology*; D005677:G(M1) Ganglioside / Q000378:metabolism*; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000378:metabolism*; D066263:Protein Aggregation, Pathological / Q000378:metabolism* / Q000473:pathology
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D008081:Liposomes; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C074636:amyloid beta-protein (25-35); D005677:G(M1) Ganglioside
keywords: Amyloid aggregation; Amyloid β-peptide; Lipid raft; Membrane heterogeneity; Model membrane