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American Journal of Pathology, Vol 150, 1531-1536, Copyright © 1997 by American Society for Investigative Pathology

REGULAR ARTICLES

Charge-based binding of complement component C1q to the Alzheimer amyloid beta-peptide

S Webster, B Bonnell and J Rogers
Sun Health Research Institute, Sun City, AZ 85372, USA.

Activation of the classical pathway in Alzheimer's disease derives from the binding of the first protein, subcomponent C1q, to the amyloid beta- peptide (A beta). Analysis of the binding of C1q to A beta by competitive enzyme-linked immunosorbent assay shows that A beta fragments 1-16 and 1-28 but not 12-28 and 17-42 are capable of inhibiting the A beta/C1q interaction, implicating the A beta 1-11 region as the C1q binding site. Binding is also shown to be inhibited by conditions of high ionic strength, suggesting that charged side chains in the A beta 1-11 region are critical to the A beta/c1q interaction. Ultrastructural evidence of binding is provided by platinum replica electron microscopy. Along with a previous demonstration of the 14-26 region of the C1q A chain as the A beta binding site, these findings suggest that attractions between a negative charge cluster in A beta 1-11 and a positive charge cluster in C1qA14-26 mediate the binding of A beta and C1q.

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