AUTHOR=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 TITLE=Beneficial Effect of a Selective Adenosine A2A Receptor Antagonist in the APPswe/PS1dE9 Mouse Model of Alzheimer’s Disease JOURNAL=Frontiers in Molecular Neuroscience VOLUME=11 YEAR=2018 URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2018.00235 DOI=10.3389/fnmol.2018.00235 ISSN=1662-5099 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.