Immunization reverses memory deficits without reducing brain Aβ burden in Alzheimer's disease model
Abstract
We have previously shown that chronic treatment with the monoclonal antibody m266, which is specific for amyloid beta-peptide (Abeta), increases plasma concentrations of Abeta and reduces Abeta burden in the PDAPP transgenic mouse model of Alzheimer's disease (AD). We now report that administration of m266 to PDAPP mice can rapidly reverse memory deficits in both an object recognition task and a holeboard learning and memory task, but without altering brain Abeta burden. We also found that an Abeta/antibody complex was present in both the plasma and the cerebrospinal fluid of m266-treated mice. Our data indicate that passive immunization with this anti-Abeta monoclonal antibody can very rapidly reverse memory impairment in certain learning and memory tasks in the PDAPP mouse model of AD, owing perhaps to enhanced peripheral clearance and (or) sequestration of a soluble brain Abeta species.
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The oligomer hypothesis predicted that early memory loss should be reversible, and this prediction was confirmed in transgenic mouse experiments.
“Based on a central role for impaired signaling, the oligomer hypothesis predicted that early memory loss should be reversible. This prediction was confirmed in the transgenic mouse experiments mentioned above (Dodart et al., 2002; Kotilinek et al., 2002).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Dodart et al., 2002
Memory loss was reversed in APP transgenic mice injected with antibodies against Aβ, and this reversal did not require removal of amyloid plaques.
“Dodart, Paul and colleagues found that memory loss was reversed in APP tg-mice injected with antibodies against Aβ and that this reversal, moreover, did not require removal of amyloid plaques (Dodart et al., 2002).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Dodart et al., 2002
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References 24 · Cited by 858
- Authors
- Dodart, J.-C., Bales, K. R., Gannon, K. S., Greene, S. J., DeMattos, R. B., Mathis, C., DeLong, C. A., Wu, S., Wu, X., Holtzman, D. M., & Paul, S. M.
- Affiliations
- Eli Lilly (United States) (US)
- Washington University in St. Louis (US)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Paul, Steven M.
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2002-04-08
- Volume
- 5
- Issue
- 5
- Pages
- 452-457
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2009174342
- Cited by
- 858
- References
- 24
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 3 · 2023: 7 · 2022: 9 · 2021: 10 · 2020: 11 · 2019: 13 · 2018: 27 · 2017: 24 · 2016: 23 · 2015: 32 · 2014: 51 · 2013: 35 · 2012: 45
- FWCI
- 37.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, passive immunization, anti-amyloid beta monoclonal antibody, amyloid-beta, memory impairment, learning and memory, cerebrospinal fluid, plasma amyloid-beta, object recognition
- MeSH terms
- Alzheimer Disease, Animals, Antibodies, Monoclonal, Antigen-Antibody Complex, Behavior, Animal, Brain, Disease Models, Animal, Dose-Response Relationship, Drug, Immunization, Passive, Immunotherapy, Learning, Memory Disorders, Mice, Transgenic, Amyloid beta-Peptides, Recognition, Psychology, Mice
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