Complement C1q does not bind monomeric beta-amyloid.
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.
Snyder
S W
SW
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064.
Wang
G T
GT
Barrett
L
L
Ladror
U S
US
Casuto
D
D
Lee
C M
CM
Krafft
G A
GA
Holzman
R B
RB
Holzman
T F
TF
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
D016229:Amyloid beta-Peptides; D007074:Immunoglobulin G; D014966:Xanthenes; D015922:Complement C1q