Deposition of amyloid β-peptide (Aβ) into amyloid plaques is one of the invariant neuropathological features of Alzheimer's disease. Proteins that codeposit with Aβ are potentially important for the pathogenesis, and a recently discovered plaque-associated protein is the collagenous Alzheimer amyloid plaque component (CLAC). In this study, we investigated the molecular interactions between Aβ aggregates and CLAC using surface plasmon resonance spectroscopy and a solid-phase binding immunoassay. We found that CLAC binds to Aβ with high affinity, that the central region of Aβ is necessary and sufficient for CLAC interaction, and that the aggregation state of Aβ as well as the presence of negatively charged residues is important. We also show that this binding results in a reduced rate of fibril elongation. Taken together, we suggest that CLAC becomes involved at an intermediate stage in the pathogenesis by binding to Aβ fibrils, including fibrils formed from peptides with truncated N- or C-termini, and ther...