Abstract
In Alzheimerss disease (AD) a disturbed balance between synthesis and removal of Aβ leads to the formation of Aβ deposits and a reaction of the innate immune system. Little evidence exists for a contribution of the adaptive immune response in AD, as no signs of influx of blood borne cells or presence of immunoglobulins in Aβ deposits are apparent. Factors of the complement (C) system and pentraxins act as pattern recognition molecules and mediate uptake of Aβ by glial cells expressing C-receptors (Crec). These interactions may, however, also lead to synthesis and secretion of reactive oxygen species (ROS), cytokines, chemokines and other potentially neurotoxic agents by the glial cells. Virtually all complement factors are produced in brain, and the expression is increased in AD affected brain areas. In AD brain areas with amyloid deposits especially classical pathway C activation products are readily observed. Also C regulatory proteins (Creg) and Crec can be found in the brain parenchyma and are upregulated, especially under acute inflammatory conditions, such as meningitis. However, under chronic low-grade inflammatory conditions, such as in AD, Creg and to some extent Crec expression may remain at a low level, thereby allowing C activation to proceed, leading to sustained activation of glial cells and neurodegenerative changes. In this review evidence from immunohistochemical, in vitro and animal studies pointing to a role for C activation is discussed, with special focus on the disturbed balance between C activators and Cregs in AD.
Keywords: Complement, complement receptors, Alzheimer's disease, amyloid, microglia, neuroinflammation, Amyloid plaques, Vascular amyloid, Cerebral amyloid angiopathy, Age related macula degeneration (AMD), Complement regulatory proteins (Creg), C1q, C1-Inhibitor, Factor H, Clusterin
Current Alzheimer Research
Title: Histological and Direct Evidence for the Role of Complement in the Neuroinflammation of AD
Volume: 8 Issue: 1
Author(s): Robert Veerhuis
Affiliation:
Keywords: Complement, complement receptors, Alzheimer's disease, amyloid, microglia, neuroinflammation, Amyloid plaques, Vascular amyloid, Cerebral amyloid angiopathy, Age related macula degeneration (AMD), Complement regulatory proteins (Creg), C1q, C1-Inhibitor, Factor H, Clusterin
Abstract: In Alzheimerss disease (AD) a disturbed balance between synthesis and removal of Aβ leads to the formation of Aβ deposits and a reaction of the innate immune system. Little evidence exists for a contribution of the adaptive immune response in AD, as no signs of influx of blood borne cells or presence of immunoglobulins in Aβ deposits are apparent. Factors of the complement (C) system and pentraxins act as pattern recognition molecules and mediate uptake of Aβ by glial cells expressing C-receptors (Crec). These interactions may, however, also lead to synthesis and secretion of reactive oxygen species (ROS), cytokines, chemokines and other potentially neurotoxic agents by the glial cells. Virtually all complement factors are produced in brain, and the expression is increased in AD affected brain areas. In AD brain areas with amyloid deposits especially classical pathway C activation products are readily observed. Also C regulatory proteins (Creg) and Crec can be found in the brain parenchyma and are upregulated, especially under acute inflammatory conditions, such as meningitis. However, under chronic low-grade inflammatory conditions, such as in AD, Creg and to some extent Crec expression may remain at a low level, thereby allowing C activation to proceed, leading to sustained activation of glial cells and neurodegenerative changes. In this review evidence from immunohistochemical, in vitro and animal studies pointing to a role for C activation is discussed, with special focus on the disturbed balance between C activators and Cregs in AD.
Export Options
About this article
Cite this article as:
Veerhuis Robert, Histological and Direct Evidence for the Role of Complement in the Neuroinflammation of AD, Current Alzheimer Research 2011; 8 (1) . https://dx.doi.org/10.2174/156720511794604589
DOI https://dx.doi.org/10.2174/156720511794604589 |
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
-
Nanomedicines as Cancer Therapeutics: Current Status
Current Cancer Drug Targets Recent Advances in Analytical Techniques used for the Determination of Fluoroquinolones in Pharmaceuticals and Samples of Biological Origin - A Review Article
Current Pharmaceutical Analysis Microemulsion and Microemulsion-Based Gels for Topical Antifungal Therapy with Phytochemicals
Current Pharmaceutical Design Revolutionary Impact of Nanodrug Delivery on Neuroscience
Current Neuropharmacology Aquaporin Water Channels in Central Nervous System
Current Neurovascular Research Toxicities of Immunosuppressive Treatment of Autoimmune Neurologic Diseases
Current Neuropharmacology Targeted Vascular Drug Delivery in Cerebral Cancer
Current Pharmaceutical Design Severe Meningococcal Infections in Children and Adolescents
Current Pediatric Reviews Management of Tuberculosis in Children and New Treatment Options
Infectious Disorders - Drug Targets Mechanisms of Drug Hypersensitivity Reactions and the Skin
Recent Patents on Inflammation & Allergy Drug Discovery Drug Development Against Sleeping Sickness: Old Wine in New Bottles?
Current Medicinal Chemistry Antioxidants and Neuroprotection in the Adult and Developing Central Nervous System
Current Medicinal Chemistry Imaging and Clinical Features of Neurocutaneous Melanosis in the Pediatric Population
Current Medical Imaging Lipid-Based Nanoparticulate Systems for the Delivery of Anti-Cancer Drug Cocktails: Implications on Pharmacokinetics and Drug Toxicities
Current Drug Metabolism Integrin α4β7 Antagonists: Activities, Mechanisms of Action and Therapeutic Prospects
Current Immunology Reviews (Discontinued) Impact of HIV on Regional & Cellular Organisation of the Brain
Current HIV Research Current Status of Carbapenem Antibiotics
Current Topics in Medicinal Chemistry Natural Compounds Therapeutic Features in Brain Disorders by Experimental, Bioinformatics and Cheminformatics Methods
Current Medicinal Chemistry Astrocytes and Inflammasome: A Possible Crosstalk in Neurological Diseases
Current Medicinal Chemistry Therapeutic Application of Melatonin in the Treatment of Melanoma: A Review
Current Cancer Therapy Reviews