title: Complement C1q does not bind monomeric beta-amyloid.
abstract: The tendency of both labeled and unlabeled beta-amyloid to bind in solution to C1q, the recognition species in the complement cascade, was examined using both hydrodynamic and spectroscopic methods. Potential binding interactions were evaluated using a purified synthetic beta-amyloid 1-40 sequence, alone, and selectively labeled at the amino terminus with spectroscopic probes. The probes permitted both absorbance and fluorescence analyses of beta-amyloid binding interactions. Under conditions used for the analyses beta-amyloid exists exclusively as a monomer in solution, and C1q retains an intact quaternary structure and is capable of binding to IgM. When mixed together the monomeric beta-amyloid does not bind to, or interact with, the complement C1q at concentrations below approximately 100 microM. The data suggest that if beta-amyloid toxicity is associated with complement activation in Alzheimer's disease then monomeric beta-amyloid is likely not responsible for activation through the classical complement pathway.
authors.affiliation: Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064.
authors.forename: S W
authors.initials: SW
authors.lastname: Snyder
authors.forename: G T
authors.initials: GT
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Barrett
authors.forename: U S
authors.initials: US
authors.lastname: Ladror
authors.forename: D
authors.initials: D
authors.lastname: Casuto
authors.forename: C M
authors.initials: CM
authors.lastname: Lee
authors.forename: G A
authors.initials: GA
authors.lastname: Krafft
authors.forename: R B
authors.initials: RB
authors.lastname: Holzman
authors.forename: T F
authors.initials: TF
authors.lastname: Holzman
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D015922:Complement C1q / Q000378:metabolism*; D004347:Drug Interactions; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D013058:Mass Spectrometry; D015394:Molecular Structure; D014966:Xanthenes / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D007074:Immunoglobulin G; D014966:Xanthenes; D015922:Complement C1q