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.
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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 |
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