The DOI matches its Crossref record; 19 of the 20 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Elevated levels of oligomers have been associated with AD, as they are found in AD brains and are considered the most toxic and pathogenic form of Aβ [4,5,6,7,18].”
From Treatment of Alzheimer’s Disease: Beyond Symptomatic Therapies (2023) · cites this paper as [18]
In the citing paper
“Generation, purification, and characterization of A11, OC, and NU-4 have been described previously.70,71”
From Microglial INPP5D limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease (2023) · cites this paper as [70]
In the citing paper
“Dot immunoblots of soluble extracts from human brain show major increases in oligomers in AD-affected tissue (Gong et al., 2003; Kayed et al., 2003; Lambert et al., 2001).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Kayed et al., 2003
In the citing paper
“Immunohistochemistry confirms that oligomers associate with neurons, accumulating very early in disease progression (Lacor et al., 2004), in loci distinct from amyloid deposits (Kayed et al., 2003).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Kayed et al., 2003
Citations
Cites
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864
Diffusible, nonfibrillar ligands derived from Aβ 1–42 are potent central nervous system neurotoxins
Lambert, M. P., Barlow, A. K., Chromy, B. A., Edwards, C., Freed, R., Liosatos, M., Morgan, T. E., Rozovsky, I., Trommer, B., Viola, K. L., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6448 · Cited by 3,506
Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases
Bucciantini, M., Giannoni, E., Chiti, F., Baroni, F., Formigli, L., Zurdo, J., Taddei, N., Ramponi, G., Dobson, C. M., & Stefani, M. (2002) · Nature · doi:10.1038/416507a · Cited by 2,434
Soluble Amyloid β Peptide Concentration as a Predictor of Synaptic Change in Alzheimer's Disease
Lue, L.-F., Kuo, Y.-M., Roher, A. E., Brachova, L., Shen, Y., Sue, L., Beach, T., Kurth, J. H., Rydel, R. E., & Rogers, J. (1999) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65184-x · Cited by 1,530
Amyloid pores from pathogenic mutations
Lashuel, H. A., Hartley, D. M., Petre, B. M., Walz, T., & Lansbury, P. T. (2002) · Nature · doi:10.1038/418291a · Cited by 1,307
Serio, T., Cashikar, A., Kowal, A., Sawicki, G., Moslehi, J., Serpell, L., Arnsdorf, M., & Lindquist, S. (2000) · Science · doi:10.1126/science.289.5483.1317 · Cited by 988
Hartley, D. M., Walsh, D. M., Ye, C. P., Diehl, T., Vasquez, S., Vassilev, P. M., Teplow, D. B., & Selkoe, D. J. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-20-08876.1999 · Cited by 817
Conway, K. A., Harper, J. D., & Lansbury, P. T. (2000) · Biochemistry · doi:10.1021/bi991447r · Cited by 786
Water-soluble Aβ(N-40, N-42) oligomers in normal and Alzheimer disease brains
Kuo, Y.-M., Emmerling, M. R., Vigo-Pelfrey, C., Kasunic, T. C., Kirkpatrick, J. B., Murdoch, G. H., Ball, M. J., & Roher, A. E. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.8.4077 · Cited by 618
Harper, J. D., Wong, S. S., Lieber, C. M., & Lansbury, P. T. (1999) · Biochemistry · doi:10.1021/bi9904149 · Cited by 454
Flagged first, then by citations
1 of the 20 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- H. A. Lashuel, D. Hartley, B. M. Petre, T. Walz, P. T. Lansbury Jr., Nature418, 291. (2002).
Cited by
Sorted by citations
Items 1,001–1,040 of 1,040
Role of amyloid beta in lipid homeostasis
Grösgen, S., Grimm, M. O. W., Frieß, P., & Hartmann, T. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2010.05.002 · Cited by 90
Tew, D. J., Bottomley, S. P., Smith, D. P., Ciccotosto, G. D., Babon, J., Hinds, M. G., Masters, C. L., Cappai, R., & Barnham, K. J. (2008) · Biophysical Journal · doi:10.1529/biophysj.107.119909 · Cited by 93
Kuszczyk, M. A., Sanchez, S., Pankiewicz, J., Kim, J., Duszczyk, M., Guridi, M., Asuni, A. A., Sullivan, P. M., Holtzman, D. M., & Sadowski, M. J. (2013) · The American Journal of Pathology · doi:10.1016/j.ajpath.2013.01.034 · Cited by 89
“Synaptotoxicity appears to concern both extracellular and intracellular Ab.”
MethodInfluentialα-Synuclein Oligomers Induce a Unique Toxic Tau Strain
Castillo-Carranza, D. L., Guerrero-Muñoz, M. J., Sengupta, U., Gerson, J. E., & Kayed, R. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.12.018 · Cited by 84
Self-citationHenríquez, G., Gomez, A., Guerrero, E., & Narayan, M. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00381 · Cited by 83
Insulin rescues amyloid β-induced impairment of hippocampal long-term potentiation
Lee, C.-C., Kuo, Y.-M., Huang, C.-C., & Hsu, K.-S. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.06.014 · Cited by 81
Molecular basis of β-amyloid oligomer recognition with a conformational antibody fragment
Morgado, I., Wieligmann, K., Bereza, M., Rönicke, R., Meinhardt, K., Annamalai, K., Baumann, M., Wacker, J., Hortschansky, P., Malešević, M., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1206433109 · Cited by 80
The neuroprotective effect of doxycycline on neurodegenerative diseases
Santa-Cecília, F. V., Leite, C. A., Del-Bel, E., & Raisman-Vozari, R. (2019) · Neurotoxicity Research · doi:10.1007/s12640-019-00015-z · Cited by 73
Castranio, E. L., Hasel, P., Haure‐Mirande, J., Ramirez Jimenez, A. V., Hamilton, B. W., Kim, R. D., Glabe, C. G., Wang, M., Zhang, B., Gandy, S., et al. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.12821 · Cited by 74
Self-citationSong, D., Jiang, X., Liu, Y., Sun, Y., Cao, S., & Zhang, Z. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00028 · Cited by 72
Protein Misfolding and Aggregation as a Therapeutic Target for Polyglutamine Diseases
Takeuchi, T., & Nagai, Y. (2017) · Brain Sciences · doi:10.3390/brainsci7100128 · Cited by 71
Cross Currents in Protein Misfolding Disorders: Interactions and Therapy
Morales, R., Green, K., & Soto, C. (2009) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152709789541998 · Cited by 72
Islets in type 2 diabetes: in honor of Dr. Robert C. Turner
Bonner-Weir, S., & O'Brien, T. D. (2008) · Diabetes · doi:10.2337/db07-1842 · Cited by 66
Muff, R., Born, W., Lutz, T. A., & Fischer, J. A. (2004) · Peptides · doi:10.1016/j.peptides.2004.08.007 · Cited by 62
Selective lowering of synapsins induced by oligomeric α-synuclein exacerbates memory deficits
Larson, M. E., Greimel, S. J., Amar, F., LaCroix, M., Boyle, G., Sherman, M. A., Schley, H., Miel, C., Schneider, J. A., Kayed, R., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1704698114 · Cited by 61
Self-citationCurrent thinking on the mechanistic basis of Alzheimer's and implications for drug development
Ising, C., Stanley, M., & Holtzman, D. (2015) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.200 · Cited by 59
Biomarkers for diseases with TDP-43 pathology
Steinacker, P., Barschke, P., & Otto, M. (2019) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2018.10.003 · Cited by 57
Modulation of the Aβ peptide aggregation pathway by KP1019 limits Aβ-associated neurotoxicity
Jones, M. R., Mu, C., Wang, M. C. P., Webb, M. I., Walsby, C. J., & Storr, T. (2015) · Metallomics · doi:10.1039/c4mt00252k · Cited by 50
Synaptic contact number and size in stratum radiatum CA1 of APP/PS1ΔE9 transgenic mice
West, M. J., Bach, G., Søderman, A., & Jensen, J. L. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.01.009 · Cited by 48
Michaud, J.-P., Richard, K. L., & Rivest, S. (2011) · Molecular Neurodegeneration · doi:10.1186/1750-1326-6-5 · Cited by 48
Ren, S., Breuillaud, L., Yao, W., Yin, T., Norris, K. A., Zehntner, S. P., & D’Adamio, L. (2021) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.016395 · Cited by 47
Capetillo-Zarate, E., Staufenbiel, M., Abramowski, D., Haass, C., Escher, A., Stadelmann, C., Yamaguchi, H., Wiestler, O. D., & Thal, D. R. (2006) · Brain · doi:10.1093/brain/awl176 · Cited by 45
Iron Redox Chemistry and Implications in the Parkinson’s Disease Brain
Abeyawardhane, D. L., & Lucas, H. R. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/4609702 · Cited by 35
Exercise prevents impaired autophagy and proteostasis in a model of neurogenic myopathy
Campos, J. C., Baehr, L. M., Gomes, K. M. S., Bechara, L. R. G., Voltarelli, V. A., Bozi, L. H. M., Ribeiro, M. A. C., Ferreira, N. D., Moreira, J. B. N., Brum, P. C., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-30365-1 · Cited by 32
Takeda, K., Uda, A., Mitsubori, M., Nagashima, S., Iwasaki, H., Ito, N., Shiiba, I., Ishido, S., Matsuoka, M., Inatome, R., et al. (2021) · Communications Biology · doi:10.1038/s42003-021-01720-2 · Cited by 32
Urano, F., Hayashi, N., Arisaka, F., Kurita, H., Murata, S., & Ichinose, H. (2006) · The Journal of Biochemistry · doi:10.1093/jb/mvj073 · Cited by 30
Lambert, M., Velasco, P., Viola, K., & Klein, W. (2009) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152709787601876 · Cited by 29
Monomeric Aβ1–42 and RAGE: key players in neuronal differentiation
Piras, S., Furfaro, A. L., Piccini, A., Passalacqua, M., Borghi, R., Carminati, E., Parodi, A., Colombo, L., Salmona, M., Pronzato, M. A., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.01.002 · Cited by 27
Reinke, A. A., Seh, H. Y., & Gestwicki, J. E. (2009) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2009.07.082 · Cited by 26
Sequence of proteome profiles in preclinical and symptomatic Alzheimer's disease
Li, X., Tsolis, K. C., Koper, M. J., Ronisz, A., Ospitalieri, S., von Arnim, C. A. F., Vandenberghe, R., Tousseyn, T., Scheuerle, A., Economou, A., et al. (2021) · Alzheimer's & Dementia · doi:10.1002/alz.12345 · Cited by 27
The N Terminus of α‐Synuclein Forms Cu II ‐Bridged Oligomers
Drew, S. C. (2015) · Chemistry – A European Journal · doi:10.1002/chem.201500236 · Cited by 26
Intracerebroventricular passive immunization with anti‐oligoAβ antibody in TgCRND8
Chauhan, N. B. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21110 · Cited by 24
Immunogenic properties of amyloid beta oligomers
Dalgediene, I., Lasickiene, R., Budvytyte, R., Valincius, G., Morkuniene, R., Borutaite, V., & Zvirbliene, A. (2013) · Journal of Biomedical Science · doi:10.1186/1423-0127-20-10 · Cited by 22
Malishev, R., Nandi, S., Kolusheva, S., Shaham-Niv, S., Gazit, E., & Jelinek, R. (2016) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2016.06.019 · Cited by 21
Biosensing strategies for amyloid‐like protein aggregates
Zhou, Y., Yan, S., Dong, W., Wu, C., Zhao, Z., Wang, R., Duo, Y., Huang, Y., Xu, D., & Jiang, C. (2024) · BMEMat · doi:10.1002/bmm2.12053 · Cited by 16
Yin, T., Yao, W., Norris, K. A., & D’Adamio, L. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101089 · Cited by 14
Yesiltepe, M., Yin, T., Tambini, M. D., Breuillaud, L., Zehntner, S. P., & D’Adamio, L. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1040576 · Cited by 6
Zhang, C., He, Y., Liu, X., Xie, J., Fang, M., Yang, X., Huang, R., Lou, Q., Li, B., Gupta, A., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02462-x · Cited by 2
Li, R., Yang, L., Lindholm, K., Konishi, Y., Yue, X., Hampel, H., Zhang, D., & Shen, Y. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.4580-03.2004 · Cited by 177
Cancer Hacks Neurodegeneration: Cystatin-C as a Bridge for Microglial Amyloid Clearance via TREM2
Zhang, Y., Li, C., & Li, C. (2026) · Research · doi:10.34133/research.1456
Metadata
- Authors
- Kayed, R., Head, E., Thompson, J. L., McIntire, T. M., Milton, S. C., Cotman, C. W., & Glabe, C. G.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Glabe, Charles G.
- Venue
- Science
- Published
- 2003-04-18
- Volume
- 300
- Issue
- 5618
- Pages
- 486-489
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2121963977
- Cited by
- 4,064
- References
- 20
- Citations by year
- 2026: 74 · 2025: 87 · 2024: 100 · 2023: 106 · 2022: 114 · 2021: 135 · 2020: 155 · 2019: 177 · 2018: 184 · 2017: 190 · 2016: 172 · 2015: 217 · 2014: 215 · 2013: 209 · 2012: 244
- FWCI
- 99.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG 16573, AG 00538, P50AG016573)
- National Institute of Neurological Disorders and Stroke (NS 31230, R01NS031230)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Health Sciences › Medicine › Internal Medicine › Amyloidosis: Diagnosis, Treatment, Outcomes
- Keywords
- amyloid conformation, oligomeric structure, amyloid toxicity, Alzheimer's disease, amyloid-beta, amyloid fibrils, pathogenesis mechanisms
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Amyloid, Animals, Antibodies, Antibody Specificity, Biopolymers, Brain, Brain Chemistry, Cell Survival, Humans, Microscopy, Electron, Peptide Fragments, Protein Conformation, Rabbits, Solubility, Tumor Cells, Cultured, Amyloid beta-Peptides, Neurofibrillary Tangles, Microscopy, Confocal, Molecular Mimicry
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
