title: Light scattering analysis of fibril growth from the amino-terminal fragment beta(1-28) of beta-amyloid peptide.
abstract: beta-Amyloid protein (beta-A/4) is the major protein component of Alzheimer disease-related senile plaques and has been postulated to be a significant contributing factor in the onset and/or progression of the disease. In the senile plaque, beta-A/4 appears as bundles of amyloid fibrils. The biological activity of beta-A/4 may be related to its state of aggregation. In this work, self-assembly, fibril formation, and interfibrillary aggregation of beta(1-28), a synthetic peptide homologous with the amino-terminal fragment of beta-A/4, were investigated. The predominant form of beta(1-28) detected by size-exclusion chromatography and polyacrylamide gel electrophoresis was apparently a tetramer which does not bind Congo red. Aggregates containing cross-beta sheet structures which bind Congo red and thioflavin T were observed at concentrations of approximately 0.3 mg/ml or greater. Concentrations of 0.5-1 mg/ml were necessary for aggregation into fibrils to be detectable by classical or quasielastic light scattering. Both fibril elongation and fibril-fibril aggregation occur over the time scale investigated. The kinetics of aggregation were much faster at physiological salt concentrations than at lower ionic strength. Ionic strength also appeared to influence the morphology of the fibril aggregates. The data indicate that sample preparation method and sample history influence fibril size and number density.
authors.affiliation: Department of Chemical Engineering, University of Wisconsin, Madison 53706.
authors.forename: C L
authors.initials: CL
authors.lastname: Shen
authors.forename: G L
authors.initials: GL
authors.lastname: Scott
authors.forename: F
authors.initials: F
authors.lastname: Merchant
authors.forename: R M
authors.initials: RM
authors.lastname: Murphy
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000648:ultrastructure; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D003224:Congo Red; D004591:Electrophoresis, Polyacrylamide Gel; D008027:Light; D008433:Mathematics; D008854:Microscopy, Electron; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012542:Scattering, Radiation; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010455:Peptides; C084358:amyloid beta-protein (1-28); D003224:Congo Red