The DOI matches its Crossref record; 44 of the 45 references it cites were found in a registry or an index.
Vaccination with soluble Aβ oligomers generates toxicity‐neutralizing antibodies
Abstract
In recent studies of transgenic models of Alzheimer's disease (AD), it has been reported that antibodies to aged beta amyloid peptide 1-42 (Abeta(1-42)) solutions (mixtures of Abeta monomers, oligomers and amyloid fibrils) cause conspicuous reduction of amyloid plaques and neurological improvement. In some cases, however, neurological improvement has been independent of obvious plaque reduction, and it has been suggested that immunization might neutralize soluble, non-fibrillar forms of Abeta. It is now known that Abeta toxicity resides not only in fibrils, but also in soluble protofibrils and oligomers. The current study has investigated the immune response to low doses of Abeta(1-42) oligomers and the characteristics of the antibodies they induce. Rabbits that were injected with Abeta(1-42) solutions containing only monomers and oligomers produced antibodies that preferentially bound to assembled forms of Abeta in immunoblots and in physiological solutions. The antibodies have proven useful for assays that can detect inhibitors of oligomer formation, for immunofluorescence localization of cell-attached oligomers to receptor-like puncta, and for immunoblots that show the presence of SDS-stable oligomers in Alzheimer's brain tissue. The antibodies, moreover, were found to neutralize the toxicity of soluble oligomers in cell culture. Results support the hypothesis that immunizations of transgenic mice derive therapeutic benefit from the immuno-neutralization of soluble Abeta-derived toxins. Analogous immuno-neutralization of oligomers in humans may be a key in AD vaccines.
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“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 Lambert et al., 2001
Citations
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Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
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Metadata
- Authors
- Lambert, M. P., Viola, K. L., Chromy, B. A., Chang, L., Morgan, T. E., Yu, J., Venton, D. L., Krafft, G. A., Finch, C. E., & Klein, W. L.
- Affiliations
- Northwestern University (US)
- University of Southern California (US)
- University of Illinois Chicago (US)
- Corresponding author
- Klein, William L.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2001-11
- Volume
- 79
- Issue
- 3
- Pages
- 595-605
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1857351893
- Cited by
- 349
- References
- 45
- Citations by year
- 2026: 12 · 2025: 8 · 2024: 4 · 2023: 11 · 2022: 6 · 2021: 8 · 2020: 15 · 2019: 10 · 2018: 5 · 2017: 11 · 2016: 6 · 2015: 10 · 2014: 18 · 2013: 20 · 2012: 20
- FWCI
- 8.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG-13499, P01 AG13138, R01AG013499)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, amyloid-beta oligomers, amyloid-beta 42, immunization, neutralizing antibodies, amyloid plaques, amyloid protofibrils, oligomer toxicity, Alzheimer's disease vaccine, transgenic mice
- MeSH terms
- Alzheimer Disease, Animals, Antibody Specificity, Epitopes, Fluorescent Antibody Technique, Hippocampus, Humans, Neurons, Peptide Fragments, Solubility, Vaccination, Amyloid beta-Peptides, PC12 Cells, Neuroprotective Agents, Rats
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