Cited by 250Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

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Active and Passive Immunotherapy for Neurodegenerative Disorders

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Brody, David L., Holtzman, David M.·2008·Annual Review of Neuroscience

DOI 10.1146/annurev.neuro.31.060407.125529PMC PMC2561172

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Abstract

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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Authors: Brody, D. L., & Holtzman, D. M.
Affiliations: Washington University in St. Louis (US)
ORCID: Brody, David L.
Holtzman, David M.
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
DOI: 10.1146/annurev.neuro.31.060407.125529
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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