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  Beneficial effect of a selective adenosine A(2A) receptor antagonist in the APPswe/PS1dE9 mouse model of Alzheimer's disease

Faivre, E., Coelho, J. E., Zornbach, K., Malik, E., Baqi, Y., Schneider, M., et al. (2018). Beneficial effect of a selective adenosine A(2A) receptor antagonist in the APPswe/PS1dE9 mouse model of Alzheimer's disease. Frontiers in Molecular Neuroscience, 11: 235. doi:10.3389/fnmol.2018.00235.

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fnmol-11-00235.pdf (Publisher version), 3MB
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 Creators:
Faivre, Emilie1, Author
Coelho, Joana E.1, Author
Zornbach, Katja2, Author
Malik, Enas1, Author
Baqi, Younis1, Author
Schneider, Marion1, Author
Cellai, Lucrezia1, Author
Carvalho, Kevin1, Author
Sebda, Sheherazade1, Author
Figeac, Martin1, Author
Eddarkaoui, Sabiha1, Author
Caillierez, Raphaelle1, Author
Chern, Yijuang1, Author
Heneka, Michael1, Author
Sergeant, Nicolas1, Author
Mueller, Christa E.1, Author
Halle, Annett2, Author
Buee, Luc1, Author
Lopes, Luisa V.1, Author
Blum, David1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Center of Advanced European Studies and Research (caesar), Max Planck Society, Ludwig-Erhard-Allee 2, 53175 Bonn, DE, ou_2173675              

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Free keywords: A2A; Alzheimer’s disease; adenosine receptor; amyloid; memory
 Abstract: Consumption of caffeine, a non-selective adenosine A2A receptor (A2AR) antagonist, reduces the risk of developing Alzheimer's disease (AD) and mitigates both amyloid and Tau lesions in transgenic mouse models of the disease. While short-term treatment with A2AR antagonists have been shown to alleviate cognitive deficits in mouse models of amyloidogenesis, impact of a chronic and long-term treatment on the development of amyloid burden, associated neuroinflammation and memory deficits has never been assessed. In the present study, we have evaluated the effect of a 6-month treatment of APPsw/PS1dE9 mice with the potent and selective A2AR antagonist MSX-3 from 3 to 9-10 months of age. At completion of the treatment, we found that the MSX-3 treatment prevented the development of memory deficits in APP/PS1dE9 mice, without significantly altering hippocampal and cortical gene expressions. Interestingly, MSX-3 treatment led to a significant decrease of Aβ1-42 levels in the cortex of APP/PS1dE9 animals, while Aβ1-40 increased, thereby strongly affecting the Aβ1-42/Aβ1-40 ratio. Together, these data support the idea that A2AR blockade is of therapeutic value for AD.

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Language(s): eng - English
 Dates: 2018-07-12
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000438402300001
DOI: 10.3389/fnmol.2018.00235
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Title: Frontiers in Molecular Neuroscience
  Abbreviation : Front Mol Neurosci
Source Genre: Journal
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Publ. Info: Lausanne, Switzerland : Frontiers Research Foundation
Pages: - Volume / Issue: 11 Sequence Number: 235 Start / End Page: - Identifier: ISSN: 1662-5099
CoNE: https://pure.mpg.de/cone/journals/resource/1662-5099