Abstract
The amyloid-β(Aβ ) cascade hypothesis of Alzheimers disease (AD) has dominated research and subsequent therapeutic drug development for over two decades. Central to this hypothesis is the observation that Aβ is elevated in AD patients and that the disease is ultimately characterized by the central deposition of insoluble senile plaques. More recent evidence, however, suggests that the presence or absence of plaque is insufficient to fully account for the deleterious role of elevated Aβ in AD. Such studies support the basis for an alternate interpretation of the Aβ cascade hypothesis. Namely, that soluble oligomers of Aβ (i.e., ADDLs) accumulate and cause functional deficits prior to overt neuronal cell death or plaque deposition. Accordingly, the following review focuses on research describing the preparation and functional activity of ADDLs in vitro and in vivo. These studies provide the basis for an alternate, ADDL-based, view of the Aβ cascade hypothesis and accounts for the disconnect between plaque burden and cognitive deficits. Possible therapeutic approaches aimed at lowering ADDLs in AD patients are also considered.
Keywords: NMDA antagonist, amyloid precursor protein, long-term potentiation (LTP), NSAID, glycosaminoglycans
Current Topics in Medicinal Chemistry
Title: The Role of Amyloid-Beta Derived Diffusible Ligands (ADDLs) in Alzheimers Disease
Volume: 6 Issue: 6
Author(s): Susan M. Catalano, Elizabeth C. Dodson, Darrell A. Henze, Joseph G. Joyce, Grant A. Krafft and Gene G. Kinney
Affiliation:
Keywords: NMDA antagonist, amyloid precursor protein, long-term potentiation (LTP), NSAID, glycosaminoglycans
Abstract: The amyloid-β(Aβ ) cascade hypothesis of Alzheimers disease (AD) has dominated research and subsequent therapeutic drug development for over two decades. Central to this hypothesis is the observation that Aβ is elevated in AD patients and that the disease is ultimately characterized by the central deposition of insoluble senile plaques. More recent evidence, however, suggests that the presence or absence of plaque is insufficient to fully account for the deleterious role of elevated Aβ in AD. Such studies support the basis for an alternate interpretation of the Aβ cascade hypothesis. Namely, that soluble oligomers of Aβ (i.e., ADDLs) accumulate and cause functional deficits prior to overt neuronal cell death or plaque deposition. Accordingly, the following review focuses on research describing the preparation and functional activity of ADDLs in vitro and in vivo. These studies provide the basis for an alternate, ADDL-based, view of the Aβ cascade hypothesis and accounts for the disconnect between plaque burden and cognitive deficits. Possible therapeutic approaches aimed at lowering ADDLs in AD patients are also considered.
Export Options
About this article
Cite this article as:
Catalano M. Susan, Dodson C. Elizabeth, Henze A. Darrell, Joyce G. Joseph, Krafft A. Grant and Kinney G. Gene, The Role of Amyloid-Beta Derived Diffusible Ligands (ADDLs) in Alzheimers Disease, Current Topics in Medicinal Chemistry 2006; 6 (6) . https://dx.doi.org/10.2174/156802606776743066
DOI https://dx.doi.org/10.2174/156802606776743066 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
- 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
-
Pharmacodynamics of Radiolabelled Anticancer Drugs for Positron Emission Tomography
Current Pharmaceutical Design Mononuclear Cell Recruitment and Inflammation in Atherosclerosis
Vascular Disease Prevention (Discontinued) Differences in Functional Brain Activation and Hippocampal Volume Among Amnestic Mild Cognitive Impairment Subtypes
Current Alzheimer Research Role of Ischemic Blood-Brain Barrier on Amyloid Plaques Development in Alzheimers Disease Brain
Current Neurovascular Research Ongoing In Vivo Studies with Cytoskeletal Drugs in Tau Transgenic Mice
Current Alzheimer Research SUBJECT INDEX TO VOLUME 1
Current Drug Targets Multitarget Therapeutic Effect of Fasudil in APP/PS1transgenic Mice
CNS & Neurological Disorders - Drug Targets Semantic Dementia: A Mini-Review
Mini-Reviews in Medicinal Chemistry MicroRNAs in Atrial Fibrillation
Current Medicinal Chemistry The Effects of Olprinone, a Phosphodiesterase 3 Inhibitor, on Systemic and Cerebral Circulation
Current Vascular Pharmacology Current Status of Drug Targets and Emerging Therapeutic Strategies in the Management of Alzheimer's Disease
Current Neuropharmacology Current Status of Carotid Stenting
Current Vascular Pharmacology New Devices for Treating Acute Ischemic Stroke
Recent Patents on CNS Drug Discovery (Discontinued) Patented In Vitro Blood-Brain Barrier Models in CNS Drug Discovery
Recent Patents on CNS Drug Discovery (Discontinued) Identification of Pharmacological Targets in Amyotrophic Lateral Sclerosis Through Genomic Analysis of Deregulated Genes and Pathways
Current Genomics Age-Related Mitochondrial Alterations without Neuronal Loss in the Hippocampus of a Transgenic Model of Alzheimer's Disease
Current Alzheimer Research Insights into the Structure, Function, and Regulation of Human Cytochrome P450 1A2
Current Drug Metabolism Antiphospholipid Syndrome: Characteristics and Obstetrical Management
Current Drug Targets Ontologies of Drug Discovery and Design for Neurology, Cardiology and Oncology
Current Pharmaceutical Design Ultrasound Diagnostic Method in Vascular Dementia: Current Concepts
Current Medical Imaging