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.
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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
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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
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