title: Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis.
abstract: Soluble oligomers are common to most amyloids and may represent the primary toxic species of amyloids, like the Abeta peptide in Alzheimer's disease (AD). Here we show that all of the soluble oligomers tested display a common conformation-dependent structure that is unique to soluble oligomers regardless of sequence. The in vitro toxicity of soluble oligomers is inhibited by oligomer-specific antibody. Soluble oligomers have a unique distribution in human AD brain that is distinct from fibrillar amyloid. These results indicate that different types of soluble amyloid oligomers have a common structure and suggest they share a common mechanism of toxicity.
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697-3900, USA.
authors.forename: Rakez
authors.initials: R
authors.lastname: Kayed
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Head
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Thompson
authors.forename: Theresa M
authors.initials: TM
authors.lastname: McIntire
authors.forename: Saskia C
authors.initials: SC
authors.lastname: Milton
authors.forename: Carl W
authors.initials: CW
authors.lastname: Cotman
authors.forename: Charles G
authors.initials: CG
authors.lastname: Glabe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000682:Amyloid / Q000737:chemistry / Q000633:toxicity; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000737:chemistry* / Q000276:immunology / Q000633:toxicity; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000918:Antibody Specificity; D001704:Biopolymers / Q000032:analysis / Q000737:chemistry / Q000633:toxicity; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D002470:Cell Survival; D006801:Humans; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D018716:Molecular Mimicry; D016874:Neurofibrillary Tangles / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011487:Protein Conformation; D011817:Rabbits; D012995:Solubility; D014407:Tumor Cells, Cultured
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D000906:Antibodies; D001704:Biopolymers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)