title: Metal-mediated formation of fibrillar ABri amyloid.
abstract: British amyloid (ABri) peptide is precipitated as amyloid fibrils in pathological lesions which are characteristic of familial British dementia. Unlike for other amyloidogenic peptides which have been implicated in neurodegenerative disease, for example, Abeta in Alzheimer's disease and alpha synuclein in Parkinson's disease, nothing is yet known as to whether metals mediate the formation of ABri amyloid fibrils. We show herein that a concentration of ABri, which had not previously been shown to spontaneously form amyloid, formed fibrils when incubated for 12 months at 37 degrees C. The additional presence of Al(III), in particular, or Fe(III) increased significantly both the number and the size of the fibrillar amyloid deposits which were very similar in appearance to amyloid described in hippocampal plaques in familial British dementia. Co-incubation of ABri with either Zn(II) or Cu(II) precipitated the peptide but did not result in the formation of amyloid fibrils.
authors.affiliation: Birchall Centre for Inorganic Chemistry and Materials Science, Lennard-Jones Laboratories, Keele University, Staffordshire ST5 5BG, UK.
authors.forename: Ayesha
authors.initials: A
authors.lastname: Khan
authors.forename: Alison E
authors.initials: AE
authors.lastname: Ashcroft
authors.forename: Olga V
authors.initials: OV
authors.lastname: Korchazhkina
authors.forename: Christopher
authors.initials: C
authors.lastname: Exley
mesh_terms: D000535:Aluminum / Q000378:metabolism; D000682:Amyloid / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D002851:Chromatography, High Pressure Liquid; D003300:Copper / Q000378:metabolism; D003704:Dementia / Q000235:genetics / Q000378:metabolism*; D004739:England; D006624:Hippocampus / Q000473:pathology; D007501:Iron / Q000378:metabolism; D008670:Metals / Q000378:metabolism*; D008970:Molecular Weight; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D017433:Protein Structure, Secondary; D021241:Spectrometry, Mass, Electrospray Ionization; D013696:Temperature; D013997:Time Factors; D015032:Zinc / Q000378:metabolism
chemical_list: D000682:Amyloid; D008670:Metals; D010446:Peptide Fragments; D003300:Copper; D000535:Aluminum; D007501:Iron; D015032:Zinc