title: Transthyretin binding to A-Beta peptide--impact on A-Beta fibrillogenesis and toxicity.
abstract: It has been suggested that transthyretin (TTR) is involved in preventing A-Beta fibrillization in Alzheimer's disease (AD). Here, we characterized the TTR/A-Beta interaction by competition binding assays. TTR binds to different A-Beta peptide species: soluble (Kd, 28 nM), oligomers and fibrils; diverse TTR variants bind differentially to A-Beta. Transmission electron microscopy (TEM) analysis demonstrated that TTR is capable of interfering with A-Beta fibrillization by both inhibiting and disrupting fibril formation. Co-incubation of the two molecules resulted in the abolishment of A-Beta toxicity. Our results confirmed TTR as an A-Beta ligand and indicated the inhibition/disruption of A-Beta fibrils as a possible mechanism underlying the protective role of TTR in AD.
authors.affiliation: Molecular Neurobiology Unit, Instituto de Biologia Molecular e Celular, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal.
authors.forename: R
authors.initials: R
authors.lastname: Costa
authors.forename: A
authors.initials: A
authors.lastname: Gonçalves
authors.forename: M J
authors.initials: MJ
authors.lastname: Saraiva
authors.forename: I
authors.initials: I
authors.lastname: Cardoso
mesh_terms: D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000648:ultrastructure; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000633:toxicity*; D001667:Binding, Competitive; D002460:Cell Line; D006801:Humans; D046529:Microscopy, Electron, Transmission; D011228:Prealbumin / Q000737:chemistry*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D011228:Prealbumin