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

Biochem Biophys Res Commun. 1995 Dec 26;217(3):869-75. doi: 10.1006/bbrc.1995.2852.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism*
  • Complement C1q / metabolism*
  • Humans
  • Peptide Fragments / metabolism
  • Protein Binding


  • Amyloid beta-Peptides
  • Peptide Fragments
  • Complement C1q