The Adenosinergic Signaling: A Complex but Promising Therapeutic Target for Alzheimer's Disease.

Lucrezia Cellai,Aude Deleau,David Blum,Victoria Gomez-Murcia,Emilie Faivre,Didier Vieau,Kevin Carvalho,Céline Mériaux,Luc Buée

doi:10.3389/fnins.2018.00520

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disorder in elderly people. AD is characterized by a progressive cognitive decline and it is neuropathologically defined by two hallmarks: extracellular deposits of aggregated β-amyloid (Aβ) peptides and intraneuronal fibrillar aggregates of hyper- and abnormally phosphorylated Tau proteins. AD results from multiple genetic and environmental risk factors. Epidemiological studies reported beneficial effects of caffeine, a non-selective adenosine receptors antagonist. In the present review, we discuss the impact of caffeine and of adenosinergic system modulation on AD, in terms of pathology and therapeutics.

Highlights

Alzheimer’s disease (AD) is the most common form of dementia, representing 70% of cases affecting more than 40 millions patients worldwide (Scheltens et al, 2016)
It is important to mention that a recent study performed in transgenic mice developing both amyloid and Tau lesions suggests that chronic caffeine consumption may lead to adverse effect notably by enhancing BPSD (Behavioral and Psychological Symptoms of Dementia)-like symptoms that may interfere with the ability of caffeine to normalize memory deficits (Baeta-Corral et al, 2018), underlying possible side effects that need to be carefully evaluated in future trials in patients
Given that chronic A1R activation favors activation effect and excitotoxicity occurrence due to receptor internalization (Blum et al, 2003) and that A2AR overactivation leads to memory impairments and AD pathology development, the benefits afforded by a chronic increase of adenosine tone (Lee et al, 2018) are presumably not mediated by receptor-mediated effects

Summary

Introduction

Alzheimer’s disease (AD) is the most common form of dementia, representing 70% of cases affecting more than 40 millions patients worldwide (Scheltens et al, 2016). Compelling epidemiologic evidences support that habitual consumption of caffeine is prone to Adenosinergic Signaling and Alzheimer’s Disease reduce cognitive decline with aging and to reduce AD risk (reviewed in Flaten et al, 2014; Cunha, 2016).

Results

Conclusion