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Adenosine pp 385-407 | Cite as

Adenosine Receptors and Alzheimer’s Disease

  • David Blum
  • Ursula Sandau
  • Cyril Laurent
  • Vânia Batalha
  • Antoine Leboucher
  • Malika Hamdane
  • Florence Pasquier
  • Detlev Boison
  • Luc Buée
  • Luísa V. Lopes
Chapter

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.

Keywords

Amyloid plaque Brain-derived neurotrophic factor Caffeine Inflammation Neurofibrillary tangle Tau protein 

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • David Blum
    • 1
    • 2
    • 3
  • Ursula Sandau
    • 4
  • Cyril Laurent
    • 1
    • 2
  • Vânia Batalha
    • 5
  • Antoine Leboucher
    • 1
    • 2
  • Malika Hamdane
    • 1
    • 2
    • 3
  • Florence Pasquier
    • 3
    • 6
  • Detlev Boison
    • 4
  • Luc Buée
    • 1
    • 2
    • 3
  • Luísa V. Lopes
    • 5
  1. 1.Inserm, U837Lille CedexFrance
  2. 2.UDSL, Jean-ierre Aubert Research Centre, Institut de Médecine Prédictive et de Recherche ThérapeutiqueUniversité Lille-Nord de FranceLilleFrance
  3. 3.CHRU-LilleLilleFrance
  4. 4.Legacy Research InstitutePortlandUSA
  5. 5.Neurosciences UnitInstituto de Medicina MolecularLisbonPortugal
  6. 6.Department NeurologyCHRU-LilleLilleFrance

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