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Amyloid β Protein Dimer-Containing Human CSF Disrupts Synaptic Plasticity: Prevention by Systemic Passive Immunization
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The current development of immunotherapy for Alzheimer's disease is based on the assumption that human-derived amyloid beta protein (Abeta) can be targeted in a similar manner to animal cell-derived or synthetic Abeta. Because the structure of Abeta depends on its source and the presence of cofactors, it is of great interest to determine whether human-derived oligomeric Abeta species impair brain function and, if so, whether or not their disruptive effects can be prevented using antibodies. We report that untreated ex vivo human CSF that contains Abeta dimers rapidly inhibits hippocampal long-term potentiation in vivo and that acute systemic infusion of an anti-Abeta monoclonal antibody can prevent this disruption of synaptic plasticity. Abeta monomer isolated from human CSF did not affect long-term potentiation. These results strongly support a strategy of passive immunization against soluble Abeta oligomers in early Alzheimer's disease.
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“Small oligomers obtained from AD-affected human brain also are active in plasticity assays (Barry et al., 2011; Klyubin et al., 2008; Li et al., 2011).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Klyubin et al., 2008
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RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
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Metadata
- Authors
- Klyubin, I., Betts, V., Welzel, A. T., Blennow, K., Zetterberg, H., Wallin, A., Lemere, C. A., Cullen, W. K., Peng, Y., Wisniewski, T., Selkoe, D. J., Anwyl, R., Walsh, D. M., & Rowan, M. J.
- Affiliations
- Trinity College Dublin (IE)
- University College Dublin (IE)
- New York University (US)
- University of Gothenburg (SE)
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-04-16
- Volume
- 28
- Issue
- 16
- Pages
- 4231-4237
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2685151
- OpenAlex
- W1970874743
- Cited by
- 321
- References
- 34
- Citations by year
- 2026: 13 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 15 · 2021: 12 · 2020: 15 · 2019: 11 · 2018: 13 · 2017: 12 · 2016: 13 · 2015: 15 · 2014: 14 · 2013: 18 · 2012: 35
- FWCI
- 27.16
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust (067660)
- European Commission
- Higher Education Authority
- Science Foundation Ireland
- National Institutes of Health (AG20245)
- National Institute on Aging (AG20245, R01AG020245)
- National Institute of Neurological Disorders and Stroke (R01NS136122)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyloid-beta, human cerebrospinal fluid, synaptic plasticity, long-term potentiation, hippocampus, passive immunization, anti-amyloid monoclonal antibodies, Alzheimer's disease, immunotherapy, amyloid-beta oligomers
- MeSH terms
- Alzheimer Disease, Animals, Antibodies, Monoclonal, Cricetulus, Cricetinae, Humans, Immunization, Passive, Male, Neuronal Plasticity, Synapses, Amyloid beta-Peptides, CHO Cells, Rats, Wistar, Long-Term Potentiation, Dimerization, Rats
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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.
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