title: The mouse C1q A-chain sequence alters beta-amyloid-induced complement activation.
abstract: In transgenic models of Alzheimer's disease (AD) neuronal loss has not been widely observed. The loss of neurons in AD may be due to chronic activation of complement (C') by beta-amyloid (A beta). A beta has been shown to activate C' by binding to a site on the C1q A-chain. The mouse A-chain sequence differs significantly from human, and a peptide based on the mouse A-chain sequence was ineffective at blocking activation of C' by A beta in contrast to the inhibition seen with the human peptide. Comparison of mouse and human serum showed that human C' was activated more effectively by A beta than was mouse C'. Therefore, additional genetic manipulations may be necessary to replicate in the murine model the inflammation and neurodegeneration that occur in AD.
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California Irvine, 92697-3900, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Webster
authors.forename: A J
authors.initials: AJ
authors.lastname: Tenner
authors.forename: T L
authors.initials: TL
authors.lastname: Poulos
authors.forename: D H
authors.initials: DH
authors.lastname: Cribbs
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D003167:Complement Activation / Q000187:drug effects / Q000502:physiology*; D015922:Complement C1q / Q000737:chemistry / Q000235:genetics* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008958:Models, Molecular; D009410:Nerve Degeneration / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D020836:Protein Structure, Quaternary; D013045:Species Specificity
chemical_list: D016229:Amyloid beta-Peptides; D007074:Immunoglobulin G; D010446:Peptide Fragments; D015922:Complement C1q