title: High resolution scanning tunnelling microscopy of the beta-amyloid protein (Abeta1-40) of Alzheimer's disease suggests a novel mechanism of oligomer assembly.
abstract: The aggregation of the beta-amyloid protein (Abeta) is an important step in the pathogenesis of Alzheimer's disease. There is increasing evidence that lower molecular weight oligomeric forms of Abeta may be the most toxic species in vivo. However, little is known about the structure of Abeta oligomers. In this study, scanning tunnelling microscopy (STM) was used to examine the structure of Abeta monomers, dimers and oligomers. Abeta1-40 was visualised by STM on a surface of atomically flat gold. At low concentrations (0.5 microM) small globular structures were observed. High resolution STM of these structures revealed them to be monomers of Abeta. The monomers measured approximately 3-4 nm in diameter. Internal structure was seen in many of the monomers consistent with a conformation in which the polypeptide chain is folded into 3 or 4 domains. Oligomers were seen after ageing the Abeta solution for 24 h. The oligomers were also 3-4 nm in width and appeared to be formed by the end-to-end association of monomers with the polypeptide chain oriented at 90 degrees to the axis of the oligomer. The results suggest that the oligomer formation can proceed through a mechanism involving the linear association of monomers.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Vic. 3800, Australia.
authors.forename: Dusan
authors.initials: D
authors.lastname: Losic
authors.forename: Lisandra L
authors.initials: LL
authors.lastname: Martin
authors.forename: Adam
authors.initials: A
authors.lastname: Mechler
authors.forename: Marie-Isabel
authors.initials: MI
authors.lastname: Aguilar
authors.forename: David H
authors.initials: DH
authors.lastname: Small
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D016252:Microscopy, Scanning Tunneling / Q000379:methods*; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011108:Polymers; C078592:amyloid beta-protein (1-40)