title: Preparation of stable amyloid β-protein oligomers of defined assembly order.
abstract: Oligomeric assemblies of the amyloid β-protein, Aβ, are thought to be the proximate neurotoxic agents in Alzheimer's disease (AD). Oligomer formation is a complex process that produces a polydisperse population of metastable structures. For this reason, formal structure-activity correlations, both in vitro and in vivo, have been difficult to accomplish. An analytical solution to this problem was provided by the application of a photochemical cross-linking method to the Aβ assembly system. This method, photo-induced cross-linking of unmodified proteins (PICUP), enabled the quantitative determination of the oligomer size distribution. We report here the integration of PICUP with SDS-PAGE and alkaline extraction procedures to create a method for the isolation of pure populations of oligomers of defined order. This method has been used successfully to provide material for formal structure-activity studies of Aβ oligomers.
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Clark
authors.initials: C
authors.lastname: Rosensweig
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Ono
authors.forename: Kazuma
authors.initials: K
authors.lastname: Murakami
authors.forename: Devin K
authors.initials: DK
authors.lastname: Lowenstein
authors.forename: Gal
authors.initials: G
authors.lastname: Bitan
authors.forename: David B
authors.initials: DB
authors.lastname: Teplow
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000302:isolation & purification; D004591:Electrophoresis, Polyacrylamide Gel; D006863:Hydrogen-Ion Concentration; D010446:Peptide Fragments / Q000737:chemistry* / Q000302:isolation & purification; D055668:Photochemical Processes; D055503:Protein Multimerization / Q000528:radiation effects*; D055550:Protein Stability / Q000528:radiation effects
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)