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Active and Passive Immunotherapy for Neurodegenerative Disorders
Open accessAbstract
Immunotherapeutic strategies to combat neurodegenerative disorders have galvanized the scientific community since the first dramatic successes in mouse models recreating aspects of Alzheimer disease (AD) were reported. However, initial human trials of active amyloid-beta (Abeta) vaccination were halted early because of a serious safety issue: meningoencephalitis in 6% of subjects. Nonetheless, some encouraging preliminary data were obtained, and rapid progress has been made toward developing alternative, possibly safer active and passive immunotherapeutic approaches for several neurodegenerative conditions. Many of these are currently in human trials for AD. Despite these advances, our understanding of the essential mechanisms underlying the effects seen in preclinical models and human subjects is still incomplete. Antibody-induced phagocytosis of pathological protein deposits, direct antibody-mediated disruption of aggregates, neutralization of toxic soluble proteins, a shift in equilibrium toward efflux of specific proteins from the brain, cell-mediated immune responses, and other mechanisms may all play roles depending on the specific immunotherapeutic scenario.
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“Certain types of active and passive immunization have resulted in significant side effects such as brain edema and hemorrhages (Brody and Holtzman, 2008).”
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 Brody and Holtzman, 2008
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“Previously, a variety of different anti-Aβ antibodies have been shown to inhibit Aβ accumulation in mouse models of Aβ amyloidosis, and they are considered promising disease-modifying therapies (Brody and Holtzman, 2008; Golde et al., 2009).”
From Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis (2012) · cites this paper as Brody and Holtzman, 2008
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“Previous studies have demonstrated that anti-Aβ antibodies can effectively decrease amyloid accumulation when they are given preventatively, but they are less effective in a treatment mode (Brody and Holtzman, 2008; Golde et al., 2009).”
From Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis (2012) · cites this paper as Brody and Holtzman, 2008
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Metadata
- Authors
- Brody, D. L., & Holtzman, D. M.
- Affiliations
- Washington University in St. Louis (US)
- Venue
- Annual Review of Neuroscience
- Publisher
- Annual Reviews
- Published
- 2008-07-01
- Volume
- 31
- Issue
- 1
- Pages
- 175-193
- ISSN
- 0147-006X (ISSN-L)
- 1545-4126
- PMC
- PMC2561172
- OpenAlex
- W2100298346
- Cited by
- 250
- References
- 90
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 5 · 2023: 7 · 2022: 8 · 2021: 6 · 2020: 9 · 2019: 7 · 2018: 6 · 2017: 6 · 2016: 10 · 2015: 13 · 2014: 17 · 2013: 19 · 2012: 22
- FWCI
- 3.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5k08ns049237-05)
- National Institute on Aging (AG20222, R01AG020222, R01AG013956, R37AG013956, AG13956)
- National Institute of Neurological Disorders and Stroke (NS049237, K08-NS049237)
- 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
- neurodegenerative diseases, Alzheimer's disease, active immunotherapy, passive immunotherapy, meningoencephalitis, antibody-mediated phagocytosis, cell-mediated immunity, immunotherapy safety
- MeSH terms
- Animals, Antibodies, Humans, Immunity, Immunization, Passive, Nerve Tissue Proteins, Vaccination, Amyloid beta-Peptides, Immunotherapy, Active, Neurodegenerative Diseases
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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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