Abstract
Alzheimer’s disease (AD), the most common human neurodegenerative disease, is characterized pathologically by numerous deposits of amyloid plaques in the brain. Systemic administration of clioquinol (CQ) and inoculation with amyloid-beta42 (Aβ42) vaccines have been demonstrated to significantly inhibit deposits of amyloid in AD brains. However, each of these treatments has also been reported to be neurotoxic. The generation of transgenic mice models of AD has made it possible to study aspects of this disease employing experimental animals. In the present study, we investigated the efficacy and toxicity of CQ and Aβ42 vaccine in a transgenic AD (APP/PS1) mouse model. Our results confirmed that both CQ and Aβ42 vaccine were effective in significantly reducing the deposits of amyloid in the brains of transgenic AD mice. We also report here that systemic CQ induces myelinopathies in the dorsal lateral geniculate nucleus (DLG), which was almost devoid of amyloid plaques and is the primary site of retinal efferent projections via the optic nerve. This is the first report that systemic administration of CQ causes myelinopathies in the central nervous system (CNS) of a transgenic AD mouse model as well as wild-type mice. Inoculation with an Aβ42 vaccine was also found, for the first time, to result in a significant increase in plaque-independent astrocytic hyperplasia in the dorsal part of the lateral septal nucleus (LSD) which was also devoid of plaques, reflecting potential brain inflammatory processes.
Keywords: Alzheimer’s disease, amyloid plaque, transgenic mice, clioquinol, amyloid-beta42 vaccine, myelinopathy, astrocytes.
Current Alzheimer Research
Title:Efficacy and Toxicity of Clioquinol Treatment and A-beta42 Inoculation in the APP/PSI Mouse Model of Alzheimer's Disease
Volume: 10 Issue: 5
Author(s): Yi-Hong Zhang, James Raymick, Sumit Sarkar, Debomoy K. Lahiri, Balmiki Ray, David Holtzman, Melanie Dumas and Larry C. Schmued
Affiliation:
Keywords: Alzheimer’s disease, amyloid plaque, transgenic mice, clioquinol, amyloid-beta42 vaccine, myelinopathy, astrocytes.
Abstract: Alzheimer’s disease (AD), the most common human neurodegenerative disease, is characterized pathologically by numerous deposits of amyloid plaques in the brain. Systemic administration of clioquinol (CQ) and inoculation with amyloid-beta42 (Aβ42) vaccines have been demonstrated to significantly inhibit deposits of amyloid in AD brains. However, each of these treatments has also been reported to be neurotoxic. The generation of transgenic mice models of AD has made it possible to study aspects of this disease employing experimental animals. In the present study, we investigated the efficacy and toxicity of CQ and Aβ42 vaccine in a transgenic AD (APP/PS1) mouse model. Our results confirmed that both CQ and Aβ42 vaccine were effective in significantly reducing the deposits of amyloid in the brains of transgenic AD mice. We also report here that systemic CQ induces myelinopathies in the dorsal lateral geniculate nucleus (DLG), which was almost devoid of amyloid plaques and is the primary site of retinal efferent projections via the optic nerve. This is the first report that systemic administration of CQ causes myelinopathies in the central nervous system (CNS) of a transgenic AD mouse model as well as wild-type mice. Inoculation with an Aβ42 vaccine was also found, for the first time, to result in a significant increase in plaque-independent astrocytic hyperplasia in the dorsal part of the lateral septal nucleus (LSD) which was also devoid of plaques, reflecting potential brain inflammatory processes.
Export Options
About this article
Cite this article as:
Zhang Yi-Hong, Raymick James, Sarkar Sumit, Lahiri Debomoy K., Ray Balmiki, Holtzman David, Dumas Melanie and Schmued Larry C., Efficacy and Toxicity of Clioquinol Treatment and A-beta42 Inoculation in the APP/PSI Mouse Model of Alzheimer's Disease, Current Alzheimer Research 2013; 10 (5) . https://dx.doi.org/10.2174/1567205011310050005
DOI https://dx.doi.org/10.2174/1567205011310050005 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...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
- Announcements
Related Articles
-
Biotechnological Approaches for Control of Listeria monocytogenes in Foods
Current Biotechnology T Cell Replicative Senescence in Human Aging
Current Pharmaceutical Design Mortality and Morbidity of HIV Infected Patients Receiving HAART: A Cohort Study
Current HIV Research Idiopathic Transverse Myelitis and Neuromyelitis Optica: Clinical Profiles,Pathophysiology and Therapeutic Choices
Current Neuropharmacology Detailed Molecular Biochemistry for Novel Therapeutic Design Against Nipah and Hendra Virus: A Systematic Review
Current Molecular Pharmacology Recent Advances in the Development of Anti-Infective Prophylactic and/or Therapeutic Agents Based on Toll-Like Receptor (TLRs)
Recent Patents on Anti-Infective Drug Discovery The Amyloid Cascade Hypothesis in Alzheimer’s Disease: It’s Time to Change Our Mind
Current Neuropharmacology Interrelationships Among Gut Microbiota and Host: Paradigms, Role in Neurodegenerative Diseases and Future Prospects
CNS & Neurological Disorders - Drug Targets Anti-NMDA Receptor Encephalitis in Psychiatry
Current Psychiatry Reviews Baculovirus as Vaccine Vectors
Current Gene Therapy Silkworm as a Host of Baculovirus Expression
Current Pharmaceutical Biotechnology Plant and Animal Steroids a New Hope to Search for Antiviral Agents
Current Medicinal Chemistry Harnessing Phage Display for the Discovery of Peptide-Based Drugs and Monoclonal Antibodies
Current Medicinal Chemistry Dietary Assumption of Plant Polyphenols and Prevention of Allergy
Current Pharmaceutical Design Evasion of Ribonuclease Inhibitor as a Determinant of Ribonuclease Cytotoxicity
Current Pharmaceutical Biotechnology Regulation of Ocular Immune Responses by Corneal Epithelium
Current Immunology Reviews (Discontinued) Advances in Drug Delivery from Nose to Brain: An Overview
Current Drug Therapy Alphavirus Vectors for Gene Therapy Applications
Current Gene Therapy Rationale for Peptide and DNA Based Epitope Vaccines for Alzheimers Disease Immunotherapy
CNS & Neurological Disorders - Drug Targets Recent Advances in Marine Algal Anticoagulants
Current Medicinal Chemistry - Cardiovascular & Hematological Agents