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.
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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].”
From Treatment of Alzheimer’s Disease: Beyond Symptomatic Therapies (2023) · cites this paper as [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”
From Microglial <i>INPP5D</i> limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease (2023) · cites this paper as [70]
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).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Kayed et al., 2003
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).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as 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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