Dataset Information

Expression data from C57/6J mice (Normal), APP/PS1 mice and APP/PS1 mice treatment with HPYD

ABSTRACT: Aβ is a peptide of 39-42 amino acid residues that derived from putative intramembranous processing of amyloid precursor protein (APP) at the proposed active site of the γ-secretase/PS1 aspartyl. Aβ has been shown to aggregate and accumulate abnormally in the brain of AD (Alzheimer's disease), and extracellular amyloid plaques of Aβ peptides aggregation can trigger a cascade of pathologic events leading to nerve fiber entanglement and neuronal apoptosis protease. We used microarrays to investigate the effects of HPYD on the gene expression of APP/PS1 transgenic mice, the brain tissues of control group, model group and HPYD group mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE104249 | GEO | 2018/02/23

REPOSITORIES: GEO

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Project description:Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by a progressive cognitive decline. Epidemiological studies have suggested a protective role of caffeine consumption against age-related cognitive impairments and the risk of developing AD. Effects of caffeine have been particularly ascribed to its ability to block adenosine A2A receptors (A2ARs). Early pathological upregulation of these receptors by neurons is thought to be involved in the development of synaptic and memory deficits in AD but this remains ill-defined. To tackle this question, we employed a novel transgenic mouse model allowing to promote a neuronal upregulation of A2AR in the hippocampus of APP/PS1 mice, developing AD-like amyloidogenesis. This new model was used to determine the impact of an early upregulation of A2AR on the progression of neuropathological lesions, associated behavior and underlying mechanisms in APP/PS1 mice. Our findings revealed that the early upregulation of A2AR in the presence of an ongoing amyloid pathology exacerbates memory impairments of APP/PS1 mice. These behavioral changes were not linked to major change in the development of amyloid pathology but rather associate with an increased p-tau at neuritic plaques. Moreover, proteomic and transcriptomic analysis coupled to quantitative immunofluorescence studies indicated that neuronal impairment of the receptor promoted both neuronal- and non-neuronal autonomous alterations i.e. loss of excitatory synapses and neuroinflammatory response, respectively, both presumably accounting for the detrimental effect on memory. Overall, our results provide compelling evidence that neuronal A2AR dysfunction as seen in the brain of patients contributes to AD pathogenesis, favoring synaptic deficits promoted by both amyloid (this study) and tau lesions (our previous study). In addition to provide new insights into the complex pathophysiology of AD, the present findings underscore the potential of A2AR as a relevant therapeutic target for mitigating early synaptic loss in this neurodegenerative disorder.

Dataset Information

Expression data from C57/6J mice (Normal), APP/PS1 mice and APP/PS1 mice treatment with HPYD

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