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

Link to Article in PubMed

PubMed ID

31359456

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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