Abstract
Alzheimer’s disease (AD) is characterized by three major histopathological hallmarks: β-amyloid deposits, neurofibrillary tangles and gliosis. While neglected for decades, the neuroinflammatory processes coordinated by microglia are now accepted as etiologic events in AD evolution. Microglial cells are found in close vicinity to amyloid plaques and display various activation phenotypes determined by the expression of a wide range of cytokines, chemokines, and innate immune surface receptors. During the development of AD pathology, microglia fail to restrict amyloid plaques and may contribute to neurotoxicity and cognitive deficit. Nevertheless, under specific activation states, microglia can participate in cerebral amyloid clearance. This review focuses on the complex relationship between microglia and Aβ pathology, and highlights both deleterious and beneficial roles of microglial activation states in the context of AD. A deeper understanding of microglial biology will hopefully pave the way for next-generation AD therapeutic approaches aimed at harnessing these enigmatic innate immune cells of the central nervous system.
Keywords: Alzheimer disease, amyloid-β peptide, chemokine, cytokine, gliosis, inflammation, innate immunity, microglia, neuroinflammation, phagocytosis.
CNS & Neurological Disorders - Drug Targets
Title:Innate Immunity in Alzheimer’s Disease: A Complex Affair
Volume: 12 Issue: 5
Author(s): Marie-Victoire Guillot-Sestier and Terrence Town
Affiliation:
Keywords: Alzheimer disease, amyloid-β peptide, chemokine, cytokine, gliosis, inflammation, innate immunity, microglia, neuroinflammation, phagocytosis.
Abstract: Alzheimer’s disease (AD) is characterized by three major histopathological hallmarks: β-amyloid deposits, neurofibrillary tangles and gliosis. While neglected for decades, the neuroinflammatory processes coordinated by microglia are now accepted as etiologic events in AD evolution. Microglial cells are found in close vicinity to amyloid plaques and display various activation phenotypes determined by the expression of a wide range of cytokines, chemokines, and innate immune surface receptors. During the development of AD pathology, microglia fail to restrict amyloid plaques and may contribute to neurotoxicity and cognitive deficit. Nevertheless, under specific activation states, microglia can participate in cerebral amyloid clearance. This review focuses on the complex relationship between microglia and Aβ pathology, and highlights both deleterious and beneficial roles of microglial activation states in the context of AD. A deeper understanding of microglial biology will hopefully pave the way for next-generation AD therapeutic approaches aimed at harnessing these enigmatic innate immune cells of the central nervous system.
Export Options
About this article
Cite this article as:
Guillot-Sestier Marie-Victoire and Town Terrence, Innate Immunity in Alzheimer’s Disease: A Complex Affair, CNS & Neurological Disorders - Drug Targets 2013; 12 (5) . https://dx.doi.org/10.2174/1871527311312050008
DOI https://dx.doi.org/10.2174/1871527311312050008 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Novel Treatments in Subarachnoid Hemorrhage
The current landscape of therapeutic strategies for subarachnoid hemorrhage (SAH), a significant adverse neurological event commonly resulting from the rupture of intracranial aneurysms, is rapidly evolving. Through an in-depth exploration of the natural history of SAH, historical treatment approaches, and emerging management modalities, the present work aims to provide a ...read more
Role of glial cells in autism spectrum disorder: Molecular mechanism and therapeutic approaches
Emerging evidence suggests that glial cells may play a pivotal role in neuroanatomical and behavioral changes found in autism spectrum disorder (ASD). Many individuals with ASD experience a neuro-immune system abnormalities throughout life, which implicates a potential role of microglia in the pathogenesis of ASD. Dysfunctional astrocytes and oligodendrocytes were ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...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
Related Articles
-
Myelin Sheaths and Autoimmune Response Induced by Myelin Proteins and Alphaviruses. I. Physicochemical Background
Current Medicinal Chemistry Translating Genetic Findings into Therapy in Parkinson Disease
Recent Patents on CNS Drug Discovery (Discontinued) Galectin-9 in Cancer Therapy
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Circulating Biochemical Markers of Brain Damage in Infants Complicated by Ischemia Reperfusion Injury
Cardiovascular & Hematological Agents in Medicinal Chemistry Astrocyte Infection by HIV-1: Mechanisms of Restricted Virus Replication, and Role in the Pathogenesis of HIV-1-Associated Dementia
Current HIV Research Schistosoma mansoni Antigens as Modulators of the Allergic Inflammatory Response in Asthma
Endocrine, Metabolic & Immune Disorders - Drug Targets Neuroprotective Properties of Peroxisome Proliferator-Activated Receptor Alpha (PPARα) and its Lipid Ligands
Current Medicinal Chemistry Pathogenesis of Stroke-Like Episodes in MELAS: Analysis of Neurovascular Cellular Mechanisms
Current Neurovascular Research Health Benefits of Honey: Implications for Treating Cardiovascular Diseases
Current Nutrition & Food Science Preliminary Anti-Coxsackie Activity of Novel 1-[4-(5,6-dimethyl(H)- 1H(2H)-benzotriazol-1(2)-yl)phenyl]-3-alkyl(aryl)ureas
Medicinal Chemistry Generation of Mesenchymal Stem Cells by Blood Cell Reprogramming
Current Stem Cell Research & Therapy Current Perspective of COVID-19 on Neurology: A Mechanistic Insight
Combinatorial Chemistry & High Throughput Screening Isolation of Antibodies From Non-Human Primates for Clinical Use
Current Drug Discovery Technologies Emerging Therapies in Relapsing-Remitting Multiple Sclerosis
Reviews on Recent Clinical Trials STING Activation and its Application in Immuno-Oncology
Current Topics in Medicinal Chemistry Dementia Etiologies and Remedies in Traditional Persian Medicine; A Review of Medicinal Plants and Phytochemistry
Current Drug Metabolism Pancreatic Islet Transplantation in Type 1 Diabetes Mellitus: An Update on Recent Developments
Current Diabetes Reviews Potentiometric Sensors for Organic Analytes: Insights to Proceed to Miniaturization
Current Pharmaceutical Analysis Stem Cells Derived from Human Exfoliated Deciduous Teeth (SHED) in Neuronal Disorders: A Review
Current Stem Cell Research & Therapy Cellular Delivery In Vivo of siRNA-Based Therapeutics
Current Pharmaceutical Design