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Adenosine Receptors and Alzheimer’s Disease

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Adenosine

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Abstract

Alzheimer’s disease (AD) is the most prevalent form of dementia in the aged population. Definitive diagnosis of AD is based on the presence of senile plaques and neurofibrillary tangles that are identified in post-mortem brain specimens. The formation of these AD-specific lesions is attributed to the pathological accumulation of either extracellular amyloid beta (Aβ) peptide or intraneuronal hyperphosphorylated Tau protein. The AD brain is also characterized by astrogliosis and inflammation. Sporadic AD results from multiple genetic and environmental risk factors. Prospective, retrospective epidemiological studies and experimental findings have identified chronic caffeine consumption as a protective factor. Caffeine effects would essentially result from modulation of the adenosine system. In this frame, the present review aims to discuss the role of adenosinergic system and in particular involvement of the A2AR in AD pathology and associated cognitive impairments. We also discuss the apparent paradox in regards to A2AR blockade and the aforementioned protective effects versus the disruption of specific biochemical processes that influence hippocampal synaptic plasticity, BDNF/TrkB signaling and acetylcholine release, all being associated with AD physiopathology. As an alternative to targeting specific pathways a more effective option to treat AD may be achieved by utilizing novel treatment strategies that restore adenosine homeostasis in the diseased brain. Thus, prior to exploring the efficacy of A2AR blockade as a therapeutic option for AD, we conclude that a better understanding of adenosine signaling in AD is needed.

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Authors and Affiliations

  1. Inserm, U837, 1 place de Verdun, Lille Cedex, 59045, France

    David Blum, Cyril Laurent, Antoine Leboucher, Malika Hamdane & Luc Buée

  2. UDSL, Jean-ierre Aubert Research Centre, Institut de Médecine Prédictive et de Recherche Thérapeutique, Université Lille-Nord de France, Lille, 59045, France

    David Blum, Cyril Laurent, Antoine Leboucher, Malika Hamdane & Luc Buée

  3. CHRU-Lille, Lille, 59037, France

    David Blum, Malika Hamdane, Florence Pasquier & Luc Buée

  4. Legacy Research Institute, Portland, OR, 97232, USA

    Ursula Sandau & Detlev Boison

  5. Neurosciences Unit, Instituto de Medicina Molecular, Av. Prof. Egas Moniz, Lisbon, 1640-028, Portugal

    Vânia Batalha & Luísa V. Lopes

  6. Department Neurology, CHRU-Lille, Lille, France

    Florence Pasquier

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  1. David Blum
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  10. Luísa V. Lopes
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Correspondence to David Blum or Luísa V. Lopes .

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  1. Trinity College, 300 Summit Street, LSC 208, Hartford, 06106, USA

    Susan Masino

  2. Legacy Research Institute, Portland, OR,, 1225 NE 2nd Avenue, Portland, 97232, USA

    Detlev Boison

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Blum, D. et al. (2013). Adenosine Receptors and Alzheimer’s Disease. In: Masino, S., Boison, D. (eds) Adenosine. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3903-5_19

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