ArticleBrain : a journal of neurology2019
Exacerbation of C1q dysregulation, synaptic loss and memory deficits in tau pathology linked to neuronal adenosine A2A receptor.
Article in Brain : a journal of neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50 citing papers in PubMed, 87 citations in OpenAlex.
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- Emerging roles for innate and adaptive immunity in tauopathies.Cell reports · 2025Review
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- Complement-dependent loss of inhibitory synapses on pyramidal neurons following Toxoplasma gondii infection.Journal of neurochemistry · 2024Article
- Neuronal A2A receptor exacerbates synapse loss and memory deficits in APP/PS1 mice.Brain : a journal of neurology · 2024Article
- Adenosine and adenosine receptors in metabolic imbalance-related neurological issues.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Review
- Cell autonomous microglia defects in a stem cell model of frontotemporal dementia.medRxiv : the preprint server for health sciences · 2024Article
- Environmental enrichment attenuates depressive-like behavior in maternal rats by inhibiting neuroinflammation and apoptosis and promoting neuroplasticity.Neurobiology of stress · 2024Article
- Complement C3 From Astrocytes Plays Significant Roles in Sustained Activation of Microglia and Cognitive Dysfunctions Triggered by Systemic Inflammation After Laparotomy in Adult Male Mice.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Ketamine counteracts sevoflurane-induced depressive-like behavior and synaptic plasticity impairments through the adenosine A2A receptor/ERK pathway in rats.Molecular neurobiology · 2023Article
- Pharmacology of Adenosine Receptors: Recent Advancements.Biomolecules · 2023Review
- Adenosine ABiomolecules · 2023Article
- Caffeine for Prevention of Alzheimer's Disease: Is the ABiomolecules · 2023Review
- The role of DNA methylation in progression of neurological disorders and neurodegenerative diseases as well as the prospect of using DNA methylation inhibitors as therapeutic agents for such disorders.IBRO neuroscience reports · 2023Review
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Authors and funding
27 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulating data support the role of tau pathology in cognitive decline in ageing and Alzheimer's disease, but underlying mechanisms remain ill-defined. Interestingly, ageing and Alzheimer's disease have been associated with an abnormal upregulation of adenosine A2A receptor (A2AR), a fine tuner of synaptic plasticity. However, the link between A2AR signalling and tau pathology has remained largely unexplored. In the present study, we report for the first time a significant upregulation of A2AR in patients suffering from frontotemporal lobar degeneration with the MAPT P301L mutation. To model these alterations, we induced neuronal A2AR upregulation in a tauopathy mouse model (THY-Tau22) using a new conditional strain allowing forebrain overexpression of the receptor. We found that neuronal A2AR upregulation increases tau hyperphosphorylation, potentiating the onset of tau-induced memory deficits. This detrimental effect was linked to a singular microglial signature as revealed by RNA sequencing analysis. In particular, we found that A2AR overexpression in THY-Tau22 mice led to the hippocampal upregulation of C1q complement protein-also observed in patients with frontotemporal lobar degeneration-and correlated with the loss of glutamatergic synapses, likely underlying the observed memory deficits. These data reveal a key impact of overactive neuronal A2AR in the onset of synaptic loss in tauopathies, paving the way for new therapeutic approaches.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.