Abstract
Amyloid beta (Abeta) has been considered as a primary cause of Alzheimers disease (AD), and Abeta lowering approaches have been tested. Active immunization against Abeta is one of several promising Abeta-lowering approaches. Two mechanisms have been proposed: enhancement of microglial phagocytosis and Abeta sequestration (also called “peripheral sink”). We hypothesized that Abeta sequestration without immune modulation is sufficient to reduce the brain Abeta load and have demonstrated effective sequestration with Abeta binding agents that do not stimulate an immune reaction. Recent reports from other groups showed two other non-immune related Abeta binding agents, which have no structural relation to compounds we previously tested, reduced brain Abeta after peripheral administration. Congo red is a chemically synthesized small molecule that has binding affinity to Abeta. In the present study, we tested three Congo red derivatives in Abeta plaque-forming mice at an early pathological stage. Unfortunately, peripheral administration for three weeks did not substantially alter brain Abeta load. Optimized Abeta binding agents with high affinity to soluble Abeta are necessary for the sequestration approach.
Keywords: alzheimers disease (ad), immunization, transgenic mice, enoxaparin, brain, dmso, polyethylene glycol
Current Alzheimer Research
Title: An Aβ Sequestration Approach Using Non-Antibody Aβ Binding Agents
Volume: 2 Issue: 2
Author(s): Yasuji Matsuoka, Li Shao, Manik Debnath, John LaFrancois, Amanda Becker, Audrey Gray, Paul Aisen, Chester Mathis, William Klunk and Karen Duff
Affiliation:
Keywords: alzheimers disease (ad), immunization, transgenic mice, enoxaparin, brain, dmso, polyethylene glycol
Abstract: Amyloid beta (Abeta) has been considered as a primary cause of Alzheimers disease (AD), and Abeta lowering approaches have been tested. Active immunization against Abeta is one of several promising Abeta-lowering approaches. Two mechanisms have been proposed: enhancement of microglial phagocytosis and Abeta sequestration (also called “peripheral sink”). We hypothesized that Abeta sequestration without immune modulation is sufficient to reduce the brain Abeta load and have demonstrated effective sequestration with Abeta binding agents that do not stimulate an immune reaction. Recent reports from other groups showed two other non-immune related Abeta binding agents, which have no structural relation to compounds we previously tested, reduced brain Abeta after peripheral administration. Congo red is a chemically synthesized small molecule that has binding affinity to Abeta. In the present study, we tested three Congo red derivatives in Abeta plaque-forming mice at an early pathological stage. Unfortunately, peripheral administration for three weeks did not substantially alter brain Abeta load. Optimized Abeta binding agents with high affinity to soluble Abeta are necessary for the sequestration approach.
Export Options
About this article
Cite this article as:
Matsuoka Yasuji, Shao Li, Debnath Manik, LaFrancois John, Becker Amanda, Gray Audrey, Aisen Paul, Mathis Chester, Klunk William and Duff Karen, An Aβ Sequestration Approach Using Non-Antibody Aβ Binding Agents, Current Alzheimer Research 2005; 2 (2) . https://dx.doi.org/10.2174/1567205053585774
DOI https://dx.doi.org/10.2174/1567205053585774 |
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
-
Neuroferritinopathy: Update on Clinical Features and Pathogenesis
Current Drug Targets Applications of Artificial Neural Networks in Medical Science
Current Clinical Pharmacology Hypertension in the Elderly
Cardiovascular & Hematological Agents in Medicinal Chemistry Editorial (Thematic Issue: Immunophilins, Protein Chemistry and Cell Biology of a Promising New Class of Drug Targets – Part II)
Current Molecular Pharmacology Receptor-Binding and Pharmacokinetic Properties of Dopaminergic Agonists
Current Topics in Medicinal Chemistry Does Religiosity Protect Against Cognitive and Behavioral Decline in Alzheimers Dementia?
Current Alzheimer Research Insulin Resistance, Glycemic Control and Adiposity: Key Determinants of Healthy Lifespan
Current Alzheimer Research Small Molecule Inhibitors of Peptidylprolyl cis/trans Isomerase
Current Enzyme Inhibition Diverse Functions and Mechanisms of Pericytes in Ischemic Stroke
Current Neuropharmacology The Role of microRNA in Ischemic and Hemorrhagic Stroke
Current Drug Delivery Personalized Medicine, Bioethics and Social Responsibilities: Re-thinking the Pharmaceutical Industry to Remedy Inequities in Patient Care and International Health
Current Pharmacogenomics and Personalized Medicine Risk-Benefit Perspectives in COX-2 Blockade
Current Drug Safety The FDG-PET Revolution of Medical Imaging – Four Decades and Beyond
Current Molecular Imaging (Discontinued) Global View on Alzheimer’s Disease and Diabetes Mellitus: Threats, Risks and Treatment Alzheimer’s Disease and Diabetes Mellitus
Current Alzheimer Research Basal Ganglia Enlarged Perivascular Spaces are Linked to Cognitive Function in Patients with Cerebral Small Vessel Disease
Current Neurovascular Research Recent Developments in PET Instrumentation
Current Pharmaceutical Biotechnology Potential Role of Polyphenols in the Prevention of Cardiovascular Diseases: Molecular Bases
Current Medicinal Chemistry Astrocytes as an HIV Reservoir: Mechanism of HIV Infection
Current HIV Research Disruption of Circadian Rhythms and Delirium, Sleep Impairment and Sepsis in Critically ill Patients. Potential Therapeutic Implications for Increased Light-Dark Contrast and Melatonin Therapy in an ICU Environment
Current Pharmaceutical Design Compensatory Shift of Subcallosal Area and Paraterminal Gyrus White Matter Parameters on DTI in Patients with Alzheimer Disease
Current Alzheimer Research