Beneficial effect of a selective adenosine A2A receptor antagonist in the APPswe/PS1dE9 mouse model of Alzheimer’s disease

Emilie Faivre, Joana E. Coelho, Katja Zornbach, Enas Malik, Younis Baqi, Marion Schneider, Lucrezia Cellai, Kevin Carvalho, Shéhérazade Sebda, Martin Figeac, Sabiha Eddarkaoui, Raphaëlle Caillierez, Yijuang Chern, Michael Heneka, Nicolas Sergeant, Christa E. Müller, Annett Halle, Luc Buée, Luisa V. Lopes, David Blum

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Abstract

Consumption of caffeine, a non-selective adenosine A2Areceptor (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.

Original languageEnglish
Article number235
JournalFrontiers in Molecular Neuroscience
Volume11
DOIs
Publication statusPublished - Jul 12 2018

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Adenosine A2 Receptor Antagonists
Alzheimer Disease
Memory Disorders
Amyloid
Caffeine
Adenosine
Transgenic Mice
Gene Expression
Therapeutics

Keywords

  • A2A
  • Adenosine receptor
  • Alzheimer’s disease
  • Amyloid
  • Memory

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Beneficial effect of a selective adenosine A2A receptor antagonist in the APPswe/PS1dE9 mouse model of Alzheimer’s disease. / Faivre, Emilie; Coelho, Joana E.; Zornbach, Katja; Malik, Enas; Baqi, Younis; Schneider, Marion; Cellai, Lucrezia; Carvalho, Kevin; Sebda, Shéhérazade; Figeac, Martin; Eddarkaoui, Sabiha; Caillierez, Raphaëlle; Chern, Yijuang; Heneka, Michael; Sergeant, Nicolas; Müller, Christa E.; Halle, Annett; Buée, Luc; Lopes, Luisa V.; Blum, David.

In: Frontiers in Molecular Neuroscience, Vol. 11, 235, 12.07.2018.

Research output: Contribution to journalArticle

Faivre, E, Coelho, JE, Zornbach, K, Malik, E, Baqi, Y, Schneider, M, Cellai, L, Carvalho, K, Sebda, S, Figeac, M, Eddarkaoui, S, Caillierez, R, Chern, Y, Heneka, M, Sergeant, N, Müller, CE, Halle, A, Buée, L, Lopes, LV & Blum, D 2018, 'Beneficial effect of a selective adenosine A2A receptor antagonist in the APPswe/PS1dE9 mouse model of Alzheimer’s disease', Frontiers in Molecular Neuroscience, vol. 11, 235. https://doi.org/10.3389/fnmol.2018.00235
Faivre, Emilie ; Coelho, Joana E. ; Zornbach, Katja ; Malik, Enas ; Baqi, Younis ; Schneider, Marion ; Cellai, Lucrezia ; Carvalho, Kevin ; Sebda, Shéhérazade ; Figeac, Martin ; Eddarkaoui, Sabiha ; Caillierez, Raphaëlle ; Chern, Yijuang ; Heneka, Michael ; Sergeant, Nicolas ; Müller, Christa E. ; Halle, Annett ; Buée, Luc ; Lopes, Luisa V. ; Blum, David. / Beneficial effect of a selective adenosine A2A receptor antagonist in the APPswe/PS1dE9 mouse model of Alzheimer’s disease. In: Frontiers in Molecular Neuroscience. 2018 ; Vol. 11.
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