title: Multivalent binding of complement protein C1Q to the amyloid beta-peptide (A beta) promotes the nucleation phase of A beta aggregation.
abstract: 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 C1q 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 C1q 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 C1q, which offers multiple A beta binding sites spaced at 2-3 nm intervals, is required.
authors.affiliation: L.J. Roberts Center for Alzheimer's Research, Sun Health Research Institute, Sun City, AZ 85372, USA.
authors.forename: S
authors.initials: S
authors.lastname: Webster
authors.forename: C
authors.initials: C
authors.lastname: Glabe
authors.forename: J
authors.initials: J
authors.lastname: Rogers
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D015922:Complement C1q / Q000378:metabolism*; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D015922:Complement C1q