The DOI matches its Crossref record; 10 of the 11 references it cites were found in a registry or an index.
Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease
Abstract
One hallmark of Alzheimer disease is the accumulation of amyloid beta-peptide in the brain and its deposition as plaques. Mice transgenic for an amyloid beta precursor protein (APP) mini-gene driven by a platelet-derived (PD) growth factor promoter (PDAPP mice), which overexpress one of the disease-linked mutant forms of the human amyloid precursor protein, show many of the pathological features of Alzheimer disease, including extensive deposition of extracellular amyloid plaques, astrocytosis and neuritic dystrophy. Active immunization of PDAPP mice with human amyloid beta-peptide reduces plaque burden and its associated pathologies. Several hypotheses have been proposed regarding the mechanism of this response. Here we report that peripheral administration of antibodies against amyloid beta-peptide, was sufficient to reduce amyloid burden. Despite their relatively modest serum levels, the passively administered antibodies were able to enter the central nervous system, decorate plaques and induce clearance of preexisting amyloid. When examined in an ex vivo assay with sections of PDAPP or Alzheimer disease brain tissue, antibodies against amyloid beta-peptide triggered microglial cells to clear plaques through Fc receptor-mediated phagocytosis and subsequent peptide degradation. These results indicate that antibodies can cross the blood-brain barrier to act directly in the central nervous system and should be considered as a therapeutic approach for the treatment of Alzheimer disease and other neurological disorders.
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In the citing paper
“This finding suggests that anti-apoE antibody might modulate similar inflammatory responses, which is consistent with the effect of certain anti-Aβ antibodies (Bard et al., 2000; Wilcock et al., 2004).”
From Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis (2012) · cites this paper as Bard et al., 2000
In the citing paper
“Recruitment and activation of microglia around plaques and subsequent Aβ degradation/clearance have been proposed as one of the mechanisms by which Aβ immunotherapy decreases amyloid levels (Bard et al., 2000; Koenigsknecht-Talboo et al., 2008; Wang et al., 2011).”
From Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis (2012) · cites this paper as Bard et al., 2000
In the citing paper
“One of the major mechanisms for removal of the plaques in response to some anti-A antibodies is microglial-mediated phagocytosis (Bard et al., 2000;Demattos et al., 2012).”
From Anti-ApoE Antibody Given after Plaque Onset Decreases Aβ Accumulation and Improves Brain Function in a Mouse Model of Aβ Amyloidosis (2014) · cites this paper as Bard et al., 2000
In the citing paper
“We used mAb 10D5 direct against Aβ3–7 epitope [10], which is known to penetrate the blood–brain-barrier (BBB) and directly binds to deposited Aβ triggering microglial cells to clear Aβ plaques through Fc receptor-mediated phagocytosis [9].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [9]
In the citing paper
“The dose of 10D5 mAb used in this study was previously shown to be effective in removing Aβ plaques in PDAPP AD Tg mice expressing wild type murine apoE [9, 10, 22].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [9]
In the citing paper
“The primary mechanism of action of 10D5 mAb is based on its direct binding to deposited Aβ and stimulating Fc receptor-mediated Aβ plaque removal by activated microglia and possibly blood derived macrophages [9, 34].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [9]
In the citing paper
“In preclinical studies, the murine form of the antibody (3D6) was shown to bind to fibrillar, oligomeric, and monomeric forms of Aβ, reduce the amount of Aβ in the brain, and improve memory in transgenic mice that overproduced Aβ.4–8”
From Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease (2014) · cites this paper as [4]
In the citing paper
“In preclinical studies, the murine form of the antibody (3D6) was shown to bind to fibrillar, oligomeric, and monomeric forms of Aβ, reduce the amount of Aβ in the brain, and improve memory in transgenic mice that overproduced Aβ.4–8”
From Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease (2014) · cites this paper as [4]
In the citing paper
“In preclinical studies, the murine form of the antibody (3D6) was shown to bind to fibrillar, oligomeric, and monomeric forms of Aβ, reduce the amount of Aβ in the brain, and improve memory in transgenic mice that overproduced Aβ.4–8”
From Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease (2014) · cites this paper as [4]
In the citing paper
“Experimental therapies, such as Aβ immunotherapy [8, 53, 138, 164, 178], were not only shown to reduce cerebral Aβ, but even more importantly, to improve behavior in transgenic mouse models of AD-like cerebral β-amyloidosis.”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [8]
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Metadata
- Authors
- Bard, F., Cannon, C., Barbour, R., Burke, R.-L., Games, D., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., Kholodenko, D., Lee, M., Lieberburg, I., Motter, R., Nguyen, M., Soriano, F., Vasquez, N., Weiss, K., Welch, B., Seubert, P., Schenk, D., & Yednock, T.
- Affiliations
- Elan Pharmaceuticals, Inc. (Ireland) (IE)
- Corresponding author
- Bard, Frédérique
- Venue
- Nature Medicine
- Published
- 2000-08
- Volume
- 6
- Issue
- 8
- Pages
- 916-919
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W1567490604
- Cited by
- 2,012
- References
- 11
- Citations by year
- 2026: 23 · 2025: 36 · 2024: 38 · 2023: 41 · 2022: 49 · 2021: 32 · 2020: 73 · 2019: 46 · 2018: 41 · 2017: 48 · 2016: 76 · 2015: 66 · 2014: 107 · 2013: 89 · 2012: 107
- FWCI
- 67.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- 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, passive immunization, anti-amyloid antibodies, blood-brain barrier penetration, amyloid plaques, microglial phagocytosis, Fc receptors, PDAPP mice, amyloid precursor protein, plaque clearance, antibody therapy
- MeSH terms
- Alzheimer Disease, Animals, Antibodies, Disease Models, Animal, Humans, Immunization, Mice, Transgenic, Phagocytosis, Amyloid beta-Peptides, Mice, Plaque, Amyloid, In Vitro Techniques
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