Multivalent binding of complement protein C1Q to the amyloid beta-peptide (A beta) promotes the nucleation phase of A beta aggregation

Activation of the classical complement pathway has been proposed as a mechanism of neurodegeneration in Alzheimer's disease. This activation is a result of the binding of Clq to amyloid beta-peptide (A beta). Recent work has shown that A beta/C1q binding has an additional consequence: enhanced formation of the neurotoxic, fibrillar, cross beta-pleated A beta configuration. Here we show that Clq enhances A beta aggregation at physiologically relevant, nanomolar concentrations of the peptides, and demonstrate that the kinetics of this enhancement are consistent with a nucleating interaction. We also show that the intact, multimeric structure of Clq, which offers multiple A beta binding sites spaced at 2-3 nm intervals, is required. (C) 1995 Academic Press, Inc.