Population ageing is a major risk factor for dementia, the most prevalent being Alzheimer disease (AD). AD is a neurodegenerative disorder characterized by a progressive cognitive decline, notably impacting memory functions. Its formal diagnosis is based on the post-mortem examination of AD patients’ brains and defined by the combination of two lesions: extracellular deposition of fibrillar amyloid peptide, resulting from the abnormal cleavage of transmembrane APP precursor, and neurofibrillary tangles, characterized by intraneuronal accumulation of hyper- and abnormal phosphorylated tau protein (Tau pathology). Besides these two lesions hallmarks, neuro-inflammatory processes, mainly defined by an increase of the number and the activity of microglial and astroglial cells, are considered as a third pathological component. Although the relationships between amyloid pathology and neuro-inflammatory processes had been the subject of intense investigations, few studies has been achieved with regards to tau pathology. As a first aim of this work, neuro-inflammatory processes associated with Tau pathology has been evaluated using a transgenic mouse model mimicking AD-like Tau pathology, THY-Tau22 strain.. These mice overexpress a mutated human tau protein under the control of a neuronal promoter and progressively hippocampal tau pathology associated to memory decline. Transcriptomic, biochemical and histological evaluations revealed a progressive increase several markers of both innate and adaptive immunity in the hippocampus of THY-Tau22 transgenic mice. We notably observed a progressive rise of microglial and astrogliale reactions, the overproduction of many chemokines (CCL3, CCL4, CCL5) in association with a parenchymatous infiltration of T cells, without major disruption of blood brain barrier (BBB). These results highlight a correlation between the establishments of memory alterations and hippocampal tau pathology on the one hand, and the occurrence of a neuro-inflammatory response on the other hand. AD is a multifactorial disorder whose occurrence depends on different genetic and environmental factors. Among the latter, epidemiological studies have shown that caffeine consumption significantly reduces the risk to develop AD. Caffeine is a psychoactive drug, whose effects are mainly ascribed to the blockade of A1 and A2A adenosinergic receptors, the latter beeing known to modulate neuro-inflammatory processes. The role of A2A receptors in AD is far from understood, and relationship with tau pathology currently unknown. The second part of my PhD aimed at evaluating effects of caffeine but also of a specific A2AR blockade, using genetic and pharmacological means, towards behavioural alterations, tau pathology and neuro-inflammatory processes in THY-Tau22 model. Results obtained demonstrate that caffeine and specific A2AR blockade lead to beneficial effects towards memory dysfunction, tau hyperphosphorylation and hippocampal neuro-inflammation. These improvements are associated with beneficial neurochemical and electrophysiological changes. Theses results demonstrate for the first time a beneficial effect of caffeine and A2A receptor blockade in a mouse model of tauopathy and support that therapeutic targeting of A2A receptors could be of interest in AD.