UMMS Affiliation
Department of Medicine, Division of Infectious Diseases and Immunology
Publication Date
2019-09-02
Document Type
Article
Disciplines
Cells | Hemic and Immune Systems | Immunopathology | Immunoprophylaxis and Therapy | Lipids | Mental Disorders | Nervous System | Nervous System Diseases | Neuroscience and Neurobiology
Abstract
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.
Keywords
2-photon, Alzheimer's, amyloid-beta, microglia, neuroinflammation
Rights and Permissions
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.
DOI of Published Version
10.15252/embj.2018101064
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
Journal/Book/Conference Title
The EMBO journal
Related Resources
PubMed ID
31359456
Repository Citation
Tejera D, Mercan D, Sanchez-Caro JM, Hanan M, Greenberg D, Soreq H, Latz E, Golenbock DT, Heneka MT. (2019). Systemic inflammation impairs microglial Abeta clearance through NLRP3 inflammasome. Open Access Publications by UMass Chan Authors. https://doi.org/10.15252/embj.2018101064. Retrieved from https://escholarship.umassmed.edu/oapubs/3978
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Cells Commons, Hemic and Immune Systems Commons, Immunopathology Commons, Immunoprophylaxis and Therapy Commons, Lipids Commons, Mental Disorders Commons, Nervous System Commons, Nervous System Diseases Commons, Neuroscience and Neurobiology Commons