title: Alzheimer's disease peptide beta-amyloid interacts with fibrinogen and induces its oligomerization.
abstract: Increasing evidence supports a vascular contribution to Alzheimer's disease (AD), but a direct connection between AD and the circulatory system has not been established. Previous work has shown that blood clots formed in the presence of the β-amyloid peptide (Aβ), which has been implicated in AD, have an abnormal structure and are resistant to degradation in vitro and in vivo. In the present study, we show that Aβ specifically interacts with fibrinogen with a K(d) of 26.3 ± 6.7 nM, that the binding site is located near the C terminus of the fibrinogen β-chain, and that the binding causes fibrinogen to oligomerize. These results suggest that the interaction between Aβ and fibrinogen modifies fibrinogen's structure, which may then lead to abnormal fibrin clot formation. Overall, our study indicates that the interaction between Aβ and fibrinogen may be an important contributor to the vascular abnormalities found in AD.
authors.affiliation: Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Hyung Jin
authors.initials: HJ
authors.lastname: Ahn
authors.forename: Daria
authors.initials: D
authors.lastname: Zamolodchikov
authors.forename: Marta
authors.initials: M
authors.lastname: Cortes-Canteli
authors.forename: Erin H
authors.initials: EH
authors.lastname: Norris
authors.forename: J Fraser
authors.initials: JF
authors.lastname: Glickman
authors.forename: Sidney
authors.initials: S
authors.lastname: Strickland
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D001665:Binding Sites; D001808:Blood Vessels / Q000002:abnormalities; D005337:Fibrin / Q000737:chemistry / Q000378:metabolism; D005340:Fibrinogen / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D011485:Protein Binding; D020836:Protein Structure, Quaternary
chemical_list: D016229:Amyloid beta-Peptides; D005337:Fibrin; D005340:Fibrinogen