Cited by 4,064Alzheimer's disease research and treatmentsPrion Diseases and Protein MisfoldingAmyloidosis: Diagnosis, Treatment, Outcomes

Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis

Kayed, Rakez, Head, Elizabeth, Thompson, Jennifer L., McIntire, Theresa M., Milton, Saskia C., Cotman, Carl W., Glabe, Charles G.·2003·Science

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.

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Crossref · 10.1126/science.1079469

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19 of 19 references verified0 citation errors · 0 not checkable

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  • Elevated levels of Aβ oligomers are associated with AD, as they are found in AD brains and are considered the most toxic and pathogenic form of Aβ.

    “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].”
  • The generation, purification, and characterization of A11, OC, and NU-4 antibodies have been described previously.

    “Generation, purification, and characterization of A11, OC, and NU-4 have been described previously.70,71”
  • Dot immunoblots of soluble extracts from human brain show major increases in Aβ oligomers in AD-affected tissue.

    “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).”
  • Aβ oligomers associate with neurons, accumulating very early in disease progression, in loci distinct from amyloid deposits.

    “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).”

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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
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 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

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