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Journal of Neuroinflammation

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Open Access 01-12-2006 | Research

Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD

Authors: Carol A Colton, Ryan T Mott, Hayley Sharpe, Qing Xu, William E Van Nostrand, Michael P Vitek

Published in: Journal of Neuroinflammation | Issue 1/2006

Abstract

Background

Microglia are associated with neuritic plaques in Alzheimer disease (AD) and serve as a primary component of the innate immune response in the brain. Neuritic plaques are fibrous deposits composed of the amyloid beta-peptide fragments (Abeta) of the amyloid precursor protein (APP). Numerous studies have shown that the immune cells in the vicinity of amyloid deposits in AD express mRNA and proteins for pro-inflammatory cytokines, leading to the hypothesis that microglia demonstrate classical (Th-1) immune activation in AD. Nonetheless, the complex role of microglial activation has yet to be fully explored since recent studies show that peripheral macrophages enter an "alternative" activation state.

Methods

To study alternative activation of microglia, we used quantitative RT-PCR to identify genes associated with alternative activation in microglia, including arginase I (AGI), mannose receptor (MRC1), found in inflammatory zone 1 (FIZZ1), and chitinase 3-like 3 (YM1).

Results

Our findings confirmed that treatment of microglia with anti-inflammatory cytokines such as IL-4 and IL-13 induces a gene profile typical of alternative activation similar to that previously observed in peripheral macrophages. We then used this gene expression profile to examine two mouse models of AD, the APPsw (Tg-2576) and Tg-SwDI, models for amyloid deposition and for cerebral amyloid angiopathy (CAA) respectively. AGI, MRC1 and YM1 mRNA levels were significantly increased in the Tg-2576 mouse brains compared to age-matched controls while TNFα and NOS2 mRNA levels, genes commonly associated with classical activation, increased or did not change, respectively. Only TNFα mRNA increased in the Tg-SwDI mouse brain. Alternative activation genes were also identified in brain samples from individuals with AD and were compared to age-matched control individuals. In AD brain, mRNAs for TNFα, AGI, MRC1 and the chitinase-3 like 1 and 2 genes (CHI3L1; CHI3L2) were significantly increased while NOS2 and IL-1β mRNAs were unchanged.

Conclusion

Immune cells within the brain display gene profiles that suggest heterogeneous, functional phenotypes that range from a pro-inflammatory, classical activation state to an alternative activation state involved in repair and extracellular matrix remodeling. Our data suggest that innate immune cells in AD may exhibit a hybrid activation state that includes characteristics of classical and alternative activation.

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Title: Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD
Authors: Carol A Colton
Ryan T Mott
Hayley Sharpe
Qing Xu
William E Van Nostrand
Michael P Vitek
Publication date: 01-12-2006
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2006
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/1742-2094-3-27

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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