COMPLEMENT C1Q DOES NOT BIND MONOMERIC BETA-AMYLOID

The tendency of both labeled and unlabeled beta-amyloid to bind in sol ution to Clq, the recognition species in the complement cascade, was e xamined using both hydrodynamic and spectroscopic methods. Potential b inding interactions were evaluated using a purified synthetic beta-amy loid 1-40 sequence, alone, and selectively labeled at the amino termin us with spectroscopic probes. The probes permitted both absorbance and fluorescence analyses of beta-amyloid binding interactions. Under con ditions used for the analyses beta-amyloid exists exclusively as a mon omer in solution, and Clq retains an intact quaternary structure and i s capable of binding to IgM. When mixed together the monomeric beta-am yloid does not bind to, or interact with, the complement Clq at concen trations below similar to 100 mu M. The data suggest that if beta-amyl oid toxicity is associated with complement activation in Alzheimer's d isease then monomeric beta-amyloid is likely not responsible for activ ation through the classical complement pathway. (C) 1994 Academic Pres s, Inc.