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Common Structure of Soluble Amyloid Oligomers Implies Common Mechanism of Pathogenesis
Rakez Kayed,1Elizabeth Head,2Jennifer L. Thompson,1Theresa M. McIntire,3Saskia C. Milton,1Carl W. Cotman,2Charles G. Glabe1*
Soluble oligomers are common to most amyloids and may representthe primary toxic species of amyloids, like the Aßpeptide in Alzheimer's disease (AD). Here we show that all ofthe soluble oligomers tested display a common conformation-dependentstructure that is unique to soluble oligomers regardless ofsequence. The in vitro toxicity of soluble oligomers is inhibitedby oligomer-specific antibody. Soluble oligomers have a uniquedistribution in human AD brain that is distinct from fibrillaramyloid. These results indicate that different types of solubleamyloid oligomers have a common structure and suggest they sharea common mechanism of toxicity.
1 Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697–3900, USA. 2 Institute for Brain Aging & Dementia, University of California, Irvine, CA 92697–4540, USA. 3 Department of Chemistry, University of California, Irvine, CA 92697–2025, USA.
* To whom correspondence should be addressed. E-mail: cglabe{at}uci.edu
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Human Islet Amyloid Polypeptide Oligomers Disrupt Cell Coupling, Induce Apoptosis, and Impair Insulin Secretion in Isolated Human Islets.
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Diabetes
56, 65-71
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Mitoenergetic failure in Alzheimer disease.
M. S Parihar and G. J. Brewer (2007)
Am J Physiol Cell Physiol
292, C8-C23
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Amyloid-{beta}-Induced Pathological Behaviors Are Suppressed by Ginkgo biloba Extract EGb 761 and Ginkgolides in Transgenic Caenorhabditis elegans.
Y. Wu, Z. Wu, P. Butko, Y. Christen, M. P. Lambert, W. L. Klein, C. D. Link, and Y. Luo (2006)
J. Neurosci.
26, 13102-13113
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Soluble Amyloid Oligomers Increase Bilayer Conductance by Altering Dielectric Structure.
Y. Sokolov, J. A. Kozak, R. Kayed, A. Chanturiya, C. Glabe, and J. E. Hall (2006)
J. Gen. Physiol.
128, 637-647
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Amyloid Ion Channels: A Porous Argument or a Thin Excuse?.
D. Eliezer (2006)
J. Gen. Physiol.
128, 631-633
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Isoflurane-Induced Apoptosis: A Potential Pathogenic Link Between Delirium and Dementia.
Z. Xie, Y. Dong, U. Maeda, R. Moir, S. K. Inouye, D. J. Culley, G. Crosby, and R. E. Tanzi (2006)
J. Gerontol. A Biol. Sci. Med. Sci.
61, 1300-1306
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Inhibition of human IAPP fibril formation does not prevent beta-cell death: evidence for distinct actions of oligomers and fibrils of human IAPP.
J. J. Meier, R. Kayed, C.-Y. Lin, T. Gurlo, L. Haataja, S. Jayasinghe, R. Langen, C. G. Glabe, and P. C. Butler (2006)
Am J Physiol Endocrinol Metab
291, E1317-E1324
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Tau-dependent microtubule disassembly initiated by prefibrillar {beta}-amyloid.
M. E. King, H.-M. Kan, P. W. Baas, A. Erisir, C. G. Glabe, and G. S. Bloom (2006)
J. Cell Biol.
175, 541-546
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Selective vulnerability of different types of commissural neurons for amyloid {beta}-protein-induced neurodegeneration in APP23 mice correlates with dendritic tree morphology.
E. Capetillo-Zarate, M. Staufenbiel, D. Abramowski, C. Haass, A. Escher, C. Stadelmann, H. Yamaguchi, O. D. Wiestler, and D. R. Thal (2006)
Brain
129, 2992-3005
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DNA Polymerase-beta Is Expressed Early in Neurons of Alzheimer's Disease Brain and Is Loaded into DNA Replication Forks in Neurons Challenged with beta-Amyloid.
A. Copani, J. J. M. Hoozemans, F. Caraci, M. Calafiore, E. S. Van Haastert, R. Veerhuis, A. J. M. Rozemuller, E. Aronica, M. A. Sortino, and F. Nicoletti (2006)
J. Neurosci.
26, 10949-10957
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p25/Cyclin-Dependent Kinase 5 Induces Production and Intraneuronal Accumulation of Amyloid beta In Vivo.
J. C. Cruz, D. Kim, L. Y. Moy, M. M. Dobbin, X. Sun, R. T. Bronson, and L.-H. Tsai (2006)
J. Neurosci.
26, 10536-10541
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Neuroserpin Binds Abeta and Is a Neuroprotective Component of Amyloid Plaques in Alzheimer Disease.
K. J. Kinghorn, D. C. Crowther, L. K. Sharp, C. Nerelius, R. L. Davis, H. T. Chang, C. Green, D. C. Gubb, J. Johansson, and D. A. Lomas (2006)
J. Biol. Chem.
281, 29268-29277
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Normal-repeat-length polyglutamine peptides accelerate aggregation nucleation and cytotoxicity of expanded polyglutamine proteins.
N. Slepko, A. M. Bhattacharyya, G. R. Jackson, J. S. Steffan, J. L. Marsh, L. M. Thompson, and R. Wetzel (2006)
PNAS
103, 14367-14372
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Cytocidal Actions of Parasporin-2, an Anti-tumor Crystal Toxin from Bacillus thuringiensis.
S. Kitada, Y. Abe, H. Shimada, Y. Kusaka, Y. Matsuo, H. Katayama, S. Okumura, T. Akao, E. Mizuki, O. Kuge, et al. (2006)
J. Biol. Chem.
281, 26350-26360
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Dynamics of yeast prion aggregates in single living cells..
S. Kawai-Noma, S. Ayano, C.-G. Pack, M. Kinjo, M. Yoshida, K. Yasuda, and H. Taguchi (2006)
Genes Cells
11, 1085-1096
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Toxicity of recombinant {beta}-amyloid prefibrillar oligomers on the morphogenesis of the sea urchin Paracentrotus lividus.
R. Carrotta, M. Di Carlo, M. Manno, G. Montana, P. Picone, D. Romancino, and P. L. San Biagio (2006)
FASEB J
20, 1916-1917
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