title: CLAC binds to aggregated Abeta and Abeta fragments, and attenuates fibril elongation.
abstract: Deposition of amyloid beta-peptide (Abeta) into amyloid plaques is one of the invariant neuropathological features of Alzheimer's disease. Proteins that codeposit with Abeta 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 Abeta aggregates and CLAC using surface plasmon resonance spectroscopy and a solid-phase binding immunoassay. We found that CLAC binds to Abeta with high affinity, that the central region of Abeta is necessary and sufficient for CLAC interaction, and that the aggregation state of Abeta 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 Abeta fibrils, including fibrils formed from peptides with truncated N- or C-termini, and thereby slows their growth.
authors.affiliation: Karolinska Institutet and Sumitomo Pharmaceuticals Alzheimer Center (KASPAC), Neurotec, Karolinska Institutet, SE-141 57 Huddinge, Sweden. hiroyoshi.kakuyama@neurotec.ki.se
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Kakuyama
authors.forename: Linda
authors.initials: L
authors.lastname: Söderberg
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Horigome
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.forename: Camilla
authors.initials: C
authors.lastname: Dahlqvist
authors.forename: Jan
authors.initials: J
authors.lastname: Näslund
authors.forename: Lars O
authors.initials: LO
authors.lastname: Tjernberg
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology; D024361:Amino Acids, Basic; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001665:Binding Sites; D019281:Dimerization; D006801:Humans; D007118:Immunoassay; D007700:Kinetics; D024041:Non-Fibrillar Collagens / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D019151:Peptide Library; D011485:Protein Binding; D020349:Surface Plasmon Resonance
chemical_list: D024361:Amino Acids, Basic; D016229:Amyloid beta-Peptides; C456021:COL25A1 protein, human; D024041:Non-Fibrillar Collagens; D010446:Peptide Fragments; D019151:Peptide Library