Quantitative and Mechanistic Studies of Aβ Immunotherapy
Abstract
There is substantial and compelling evidence that aggregation and accumulation of amyloid beta protein (Abeta) plays a pivotal role in the development of Alzheimer's disease (AD); thus, numerous strategies to prevent Abeta aggregation and accumulation or to facilitate removal of preexisting deposits of Abeta are being evaluated as ways to treat or prevent AD. Pre-clinical studies in mice demonstrate the therapeutic potential of altering Abeta deposition by inducing a humoral immune response to fibrillar Abeta42 (fAbeta42) or passively administering anti-Abeta antibodies (Abs), and both passive and active anti-Abeta immunotherapeutic approaches are now being tested in humans. Although a variety of mechanisms have been postulated regarding how Abeta immunotherapy might work to attenuate or in some circumstances clear Abeta from the brain, no mechanism has been definitively proven or disproven. Herein, we will review the various mechanisms that have been postulated. In addition we will discuss how a more thorough understanding of the pharmacokinetics of anti-Abeta Abs and their effects on Abeta levels and turnover provides insight into both the therapeutic potential and limitation of Abeta immunotherapy. We will conclude with a discussion of additional experimentation required to better understand the mechanism of action of anti-Abeta Abs in AD and optimize antibody (Ab) mediated therapy for AD.
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Previous studies have demonstrated that anti-Aβ antibodies can effectively decrease amyloid accumulation when given preventatively, but they are less effective in a treatment mode.
“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 Golde et al., 2009
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.
“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 Golde et al., 2009
Experimental therapies such as Aβ immunotherapy reduce cerebral Aβ and improve behavior in transgenic mouse models of AD-like cerebral β-amyloidosis.
“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 [53]
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Open questions for Alzheimer's disease
Golde, T. E. (2014)
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Therapeutic antibodies as a Wright Brothers' airplane: Clinical proof-of-concept
Saido, T. C. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-28979-8.00015-2
- Authors
- Golde, T., Das, P., & Levites, Y.
- Affiliations
- Mayo Clinic (US)
- Mayo Clinic in Florida (US)
- Venue
- CNS & Neurological Disorders - Drug Targets
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2009-03-01
- Volume
- 8
- Issue
- 1
- Pages
- 31-49
- ISSN
- 1568-007X (ISSN-L)
- 1871-5273
- OpenAlex
- W2163202463
- Cited by
- 46
- References
- 0
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 5 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 8 · 2013: 6 · 2012: 5
- FWCI
- 2.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- CNS & Neurological Disorders - Drug Targets (publishedVersion)
- PubMed (publishedVersion)
- 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
- amyloid-beta immunotherapy, Alzheimer's disease, anti-amyloid antibodies, passive immunotherapy, active immunotherapy, amyloid-beta aggregation, amyloid-beta clearance, pharmacokinetics, mechanism of action, amyloid-beta 42
- MeSH terms
- Alzheimer Disease, Animals, Antibodies, Epitopes, Disease Models, Animal, Humans, Immunization, Mice, Transgenic, Amyloid beta-Peptides, Mice
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