title: Copper prevents amyloid-β(1-42) from forming amyloid fibrils under near-physiological conditions in vitro.
abstract: The aggregation and deposition of amyloid-β((1-42) )(Aβ(42)) in the brain is implicated in the aetiology of Alzheimer's disease (AD). While the mechanism underlying its deposition in vivo is unknown its precipitation in vitro is influenced by metal ions. For example, Aβ(42) is known to bind copper, Cu(II), in vitro and binding results in aggregation of the peptide. The biophysical properties of Cu(II)-Aβ(42) aggregates are of significant importance to their putative involvement in the amyloid cascade hypothesis of AD and are currently the subject of strong debate. In particular the question has been raised if sub- and super-stoichiometric concentrations of Cu(II) act in opposing ways in respectively accelerating and preventing amyloid fibril formation by Aβ(42). Herein we have used fluorimetry and transmission electron microscopy to provide unequivocal evidence that under near-physiological conditions both sub- and super-stoichiometric concentrations of Cu(II) prevented the assembly of Aβ(42) into ThT-positive β-sheet rich amyloid fibrils.
authors: The Birchall Centre, Lennard-Jones Laboratories, Keele University, Staffordshire, ST5 5BG, UK.
authors: Matthew
authors: M
authors: Mold
authors: Larissa
authors: L
authors: Ouro-Gnao
authors: Beata M
authors: BM
authors: Wieckowski
authors: Christopher
authors: C
authors: Exley
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D004492:Edetic Acid / Q000737:chemistry; D007477:Ions / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D007477:Ions; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D003300:Copper; D004492:Edetic Acid