Abstract
There is substantial and compelling evidence that aggregation and accumulation of amyloid β protein (Aβ) plays a pivotal role in the development of Alzheimers disease (AD); thus, numerous strategies to prevent Aβ aggregation and accumulation or to facilitate removal of preexisting deposits of Aβ are being evaluated as ways to treat or prevent AD [1, 2]. Pre-clinical studies in mice demonstrate the therapeutic potential of altering Aβ deposition by inducing a humoral immune response to fibrillar Aβ42 (fAβ42) or passively administering anti-Aβ antibodies (Abs) [3, 4], and both passive and active anti-Aβ immunotherapeutic approaches are now being tested in humans. Although a variety of mechanisms have been postulated regarding how Aβ immunotherapy might work to attenuate or in some circumstances clear Aβ 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-Aβ Abs and their effects on Aβ levels and turnover provides insight into both the therapeutic potential and limitation of Aβ immunotherapy. We will conclude with a discussion of additional experimentation required to better understand the mechanism of action of anti-Aβ Abs in AD and optimize antibody (Ab) mediated therapy for AD.
Keywords: Aβ Immunotherapy, Alzheimer's disease (AD), β protein, vaccination, Aβ amyloid
CNS & Neurological Disorders - Drug Targets
Title: Quantitative and Mechanistic Studies of Aβ Immunotherapy
Volume: 8 Issue: 1
Author(s): Todd E. Golde, Pritam Das and Yona Levites
Affiliation:
Keywords: Aβ Immunotherapy, Alzheimer's disease (AD), β protein, vaccination, Aβ amyloid
Abstract: There is substantial and compelling evidence that aggregation and accumulation of amyloid β protein (Aβ) plays a pivotal role in the development of Alzheimers disease (AD); thus, numerous strategies to prevent Aβ aggregation and accumulation or to facilitate removal of preexisting deposits of Aβ are being evaluated as ways to treat or prevent AD [1, 2]. Pre-clinical studies in mice demonstrate the therapeutic potential of altering Aβ deposition by inducing a humoral immune response to fibrillar Aβ42 (fAβ42) or passively administering anti-Aβ antibodies (Abs) [3, 4], and both passive and active anti-Aβ immunotherapeutic approaches are now being tested in humans. Although a variety of mechanisms have been postulated regarding how Aβ immunotherapy might work to attenuate or in some circumstances clear Aβ 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-Aβ Abs and their effects on Aβ levels and turnover provides insight into both the therapeutic potential and limitation of Aβ immunotherapy. We will conclude with a discussion of additional experimentation required to better understand the mechanism of action of anti-Aβ Abs in AD and optimize antibody (Ab) mediated therapy for AD.
Export Options
About this article
Cite this article as:
Golde E. Todd, Das Pritam and Levites Yona, Quantitative and Mechanistic Studies of Aβ Immunotherapy, CNS & Neurological Disorders - Drug Targets 2009; 8 (1) . https://dx.doi.org/10.2174/187152709787601830
DOI https://dx.doi.org/10.2174/187152709787601830 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Novel Treatments in Subarachnoid Hemorrhage
The current landscape of therapeutic strategies for subarachnoid hemorrhage (SAH), a significant adverse neurological event commonly resulting from the rupture of intracranial aneurysms, is rapidly evolving. Through an in-depth exploration of the natural history of SAH, historical treatment approaches, and emerging management modalities, the present work aims to provide a ...read more
Role of glial cells in autism spectrum disorder: Molecular mechanism and therapeutic approaches
Emerging evidence suggests that glial cells may play a pivotal role in neuroanatomical and behavioral changes found in autism spectrum disorder (ASD). Many individuals with ASD experience a neuro-immune system abnormalities throughout life, which implicates a potential role of microglia in the pathogenesis of ASD. Dysfunctional astrocytes and oligodendrocytes were ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Regulation of Apoptosis by Gram-Positive Bacteria: Mechanistic Diversity and Consequences for Immunity
Current Immunology Reviews (Discontinued) Novel Concepts for Anti-Infective Activity of Cytokines, Chemokines and Diverse Agents
Recent Patents on Anti-Infective Drug Discovery Nonstandard Drugs and Feasible New Interventions for Autoimmune Hepatitis: Part II
Inflammation & Allergy - Drug Targets (Discontinued) Electroporation Advances in Large Animals
Current Gene Therapy Recent Achievements in Understanding Immune Recovery of Children Treated with HAART
Current Pediatric Reviews Regulation of Cytokine Production by γδ T Cells
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Synthesis, Molecular Docking and Evaluation of 3-{4-[2-amino-4-(substitutedphenyl)-2H-[1, 3] oxazin/thiazin-6-yl} 2-phenyl-3H-quinazolin-4-one Derivatives for their Anticonvulsant Activity
Central Nervous System Agents in Medicinal Chemistry Anti-NMDA Receptor Encephalitis: Efficacy of Treatment for Male Patients and miRNA Biomarker
Current Medicinal Chemistry Dorsal Stream Dysfunction in Children. A Review and an Approach to Diagnosis and Management
Current Pediatric Reviews Impact of Latent Viral Infections in Mechanically Ventilated Patients
Current Respiratory Medicine Reviews Dengue Fever: Theories of Immunopathogenesis and Challenges for Vaccination
Inflammation & Allergy - Drug Targets (Discontinued) Drug Discovery in Enteroviral Infections
Infectious Disorders - Drug Targets Tauopathies – Focus on Changes at the Neurovascular Unit
Current Alzheimer Research An Overview on Global Trends in Nanotechnological Approaches for Alzheimer Therapy
Current Drug Metabolism Neuroprotective Actions of Flavones and Flavonols: Mechanisms and Relationship to Flavonoid Structural Features
Central Nervous System Agents in Medicinal Chemistry The Expanding Role of TNF-Receptor Super Family Member CD40 (tnfrsf5) in Autoimmune Disease: Focus on Th40 Cells
Current Immunology Reviews (Discontinued) The Main Receptors Involved in the COVID-19: A Systematic Review and Meta-Analysis
Current Medicinal Chemistry Ocular Application of Macrobiomolecules in Anti-Allergy and Anti- Inflammation
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents West Nile Virus NS2B/NS3 Protease As An Antiviral Target
Current Medicinal Chemistry Clinical, Immunological and Therapeutic Aspects of Autoimmune Encephalitis
Recent Patents on CNS Drug Discovery (Discontinued)