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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2016

Open Access 01-12-2016 | Research

Suppression of LPS-induced tau hyperphosphorylation by serum amyloid A

Authors: Jin Liu, Ding Wang, Shu-Qin Li, Yang Yu, Richard D. Ye

Published in: Journal of Neuroinflammation | Issue 1/2016

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Abstract

Background

Accumulation of hyperphosphorylated tau is a major neuropathological feature of tauopathies including Alzheimer’s disease (AD). Serum amyloid A (SAA), an acute-phase protein with cytokine-like property, has been implicated in amyloid deposition. It remains unclear whether SAA affects tau hyperphosphorylation.

Methods

Potential involvement of SAA in tau hyperphosphorylation was examined using intracerebral injection of SAA, and in Saa3 −/− mice receiving systemic administration of lipopolysaccharide (LPS). Induced SAA expression and microglial activation were evaluated in these mice using real-time PCR and/or immunofluorescence staining. Cultured primary neuronal cells were treated with condition media (CM) from SAA-stimulated primary microglial cells. The alteration in tau hyperphosphorylation was determined using Western blotting.

Results

Saa3 is the predominant form of SAA proteins induced by LPS in the mouse brain that co-localizes with neurons. Overexpression of SAA by intracerebral injection attenuated tau hyperphosphorylation in the brain. Conversely, Saa3 deficiency enhanced tau phosphorylation induced by systemic LPS administration. Intracerebral injection of SAA also induced the activation of microglia in the brains. IL-10 released to CM from SAA-stimulated microglia attenuated tau hyperphosphorylation in cultured primary neurons. IL-10 neutralizing antibody reversed the effect of SAA in the attenuation of tau phosphorylation.

Conclusions

LPS-induced expression of SAA proteins in the brain leads to the activation of microglia and release of IL-10, which in turn suppresses tau hyperphosphorylation in a mouse model of systemic inflammation.
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Metadata
Title
Suppression of LPS-induced tau hyperphosphorylation by serum amyloid A
Authors
Jin Liu
Ding Wang
Shu-Qin Li
Yang Yu
Richard D. Ye
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2016
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-016-0493-y

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