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Adenosine Receptors in Alzheimer’s Disease

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The Adenosine Receptors

Part of the book series: The Receptors ((REC,volume 34))

Abstract

Adenosine operates its effects through adenosine receptors, which have been proposed to be of particular relevance in neuropathological situations, such as Alzheimer’s disease (AD). AD is characterized by progressive cognitive impairment, synaptic and neuronal loss, formation of amyloid plaques, mainly composed by amyloid-beta (Aβ) peptides, and neurofibrillary tangles as well as neuroinflammation. Epidemiological studies concluded that the regular consumption of caffeine, a nonselective antagonist of adenosine receptors, is inversely correlated with the incidence of AD. Neurochemical data showed an increased A2AR density in the brain of AD patients, and these A2ARs interfere with memory, synaptic plasticity, Aβ production and neurofibrillary tangles formation in AD models. Accordingly, pharmacological blockade or genetic inactivation of A2AR prevents cognitive impairment and affords neuroprotection. However, either the mechanisms or the contribution of A2AR in different cell types for the onset and progression of AD are not completely understood. Until now, it was described that neuronal and astrocytic A2ARs have a role in controlling synaptic plasticity and memory, microglial A2AR modulates neuroinflammation and A2AR in peripheral cells also comes into play in neurodegenerative processes. This chapter will discuss the importance of adenosinergic system in AD patients and experimental models, providing an overview of future adenosine-based therapies.

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Acknowledgements

The authors ‘research was supported by Maratona da Saúde, the European Regional Development Fund (ERDF) through the COMPETE 2020 and Portuguese National Funds (FCT), ref POCI-01-0145-FEDER-007440 and PTDC/NEU-NMC/4154/2014 - AstroA2AR (POCI-01-0145-FEDER-016684).

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Authors and Affiliations

  1. CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

    Paula M. Canas, Rodrigo A. Cunha & Paula Agostinho

  2. FMUC-Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Rodrigo A. Cunha & Paula Agostinho

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  1. Paula M. Canas
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  2. Rodrigo A. Cunha
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  3. Paula Agostinho
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Correspondence to Paula Agostinho .

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  1. Department of Medical Sciences, University of Ferrara, Ferrara, Italy

    Pier Andrea Borea

  2. Department of Medical Sciences, University of Ferrara, Ferrara, Italy

    Katia Varani

  3. Department of Medical Sciences, University of Ferrara, Ferrara, Italy

    Stefania Gessi

  4. Department of Medical Sciences, University of Ferrara, Ferrara, Italy

    Stefania Merighi

  5. Department of Medical Sciences, University of Ferrara, Ferrara, Italy

    Fabrizio Vincenzi

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Canas, P.M., Cunha, R.A., Agostinho, P. (2018). Adenosine Receptors in Alzheimer’s Disease. In: Borea, P., Varani, K., Gessi, S., Merighi, S., Vincenzi, F. (eds) The Adenosine Receptors. The Receptors, vol 34. Humana Press, Cham. https://doi.org/10.1007/978-3-319-90808-3_11

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