The mouse C1q A-chain sequence alters beta-amyloid-induced complement activation.
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.
Webster
S D
SD
Department of Molecular Biology and Biochemistry, University of California Irvine, 92697-3900, USA.
Tenner
A J
AJ
Poulos
T L
TL
Cribbs
D H
DH
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
D016229:Amyloid beta-Peptides; D007074:Immunoglobulin G; D010446:Peptide Fragments; D015922:Complement C1q