Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis.
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.
Kayed
Rakez
R
Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697-3900, USA.
Head
Elizabeth
E
Thompson
Jennifer L
JL
McIntire
Theresa M
TM
Milton
Saskia C
SC
Cotman
Carl W
CW
Glabe
Charles G
CG
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
D000682:Amyloid; D016229:Amyloid beta-Peptides; D000906:Antibodies; D001704:Biopolymers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)