Systemic inflammation impairs microglial Abeta clearance through NLRP3 inflammasome
Authors
Tejera, DarioMercan, Dilek
Sanchez-Caro, Juan M.
Hanan, Mor
Greenberg, David
Soreq, Hermona
Latz, Eicke
Golenbock, Douglas T.
Heneka, Michael T.
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2019-09-02Keywords
2-photonAlzheimer's
amyloid-beta
microglia
neuroinflammation
Cells
Hemic and Immune Systems
Immunopathology
Immunoprophylaxis and Therapy
Lipids
Mental Disorders
Nervous System
Nervous System Diseases
Neuroscience and Neurobiology
Metadata
Show full item recordAbstract
Alzheimer's disease is the most prevalent type of dementia and is caused by the deposition of extracellular amyloid-beta and abnormal tau phosphorylation. Neuroinflammation has emerged as an additional pathological component. Microglia, representing the brain's major innate immune cells, play an important role during Alzheimer's. Once activated, microglia show changes in their morphology, characterized by a retraction of cell processes. Systemic inflammation is known to increase the risk for cognitive decline in human neurogenerative diseases including Alzheimer's. Here, we assess for the first time microglial changes upon a peripheral immune challenge in the context of aging and Alzheimer's in vivo, using 2-photon laser scanning microscopy. Microglia were monitored at 2 and 10 days post-challenge by lipopolysaccharide. Microglia exhibited a reduction in the number of branches and the area covered at 2 days, a phenomenon that resolved at 10 days. Systemic inflammation reduced microglial clearance of amyloid-beta in APP/PS1 mice. NLRP3 inflammasome knockout blocked many of the observed microglial changes upon lipopolysaccharide, including alterations in microglial morphology and amyloid pathology. NLRP3 inhibition may thus represent a novel therapeutic target that may protect the brain from toxic peripheral inflammation during systemic infection.Source
EMBO J. 2019 Sep 2;38(17):e101064. doi: 10.15252/embj.2018101064. Epub 2019 Jul 30. Link to article on publisher's site
DOI
10.15252/embj.2018101064Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41190PubMed ID
31359456Related Resources
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Copyright 2019 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.15252/embj.2018101064
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Except where otherwise noted, this item's license is described as Copyright 2019 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.