% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Carvalho:144978,
      author       = {Carvalho, Kevin and Faivre, Emilie and Pietrowski, Marie J
                      and Marques, Xavier and Gomez-Murcia, Victoria and Deleau,
                      Aude and Huin, Vincent and Hansen, Jan N and Kozlov,
                      Stanislav and Danis, Clément and Temido-Ferreira, Mariana
                      and Coelho, Joana E and Mériaux, Céline and Eddarkaoui,
                      Sabiha and Gras, Stéphanie Le and Dumoulin, Mélanie and
                      Cellai, Lucrezia and Landrieu, Isabelle and Chern, Yijuang
                      and Hamdane, Malika and Buée, Luc and Boutillier,
                      Anne-Laurence and Levi, Sabine and Halle, Annett and Lopes,
                      Luisa V and Blum, David},
      collaboration = {Bank, NeuroCEB Brain},
      title        = {{E}xacerbation of {C}1q dysregulation, synaptic loss and
                      memory deficits in tau pathology linked to neuronal
                      adenosine {A}2{A} receptor.},
      journal      = {Brain},
      volume       = {142},
      number       = {11},
      issn         = {0006-8950},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DZNE-2020-00342},
      pages        = {3636-3654},
      year         = {2019},
      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.},
      keywords     = {Animals / Autopsy / Complement C1q: metabolism /
                      Frontotemporal Lobar Degeneration: genetics / Frontotemporal
                      Lobar Degeneration: metabolism / Hippocampus: metabolism /
                      Hippocampus: pathology / Humans / Memory Disorders: etiology
                      / Memory Disorders: psychology / Mice / Mice, Transgenic /
                      Mutation / Neurons: metabolism / Receptor, Adenosine A2A:
                      genetics / Receptor, Adenosine A2A: metabolism / Spatial
                      Learning / Synapses: pathology / Tauopathies: genetics /
                      Tauopathies: pathology / Tauopathies: psychology / tau
                      Proteins: genetics / ADORA2A protein, human (NLM Chemicals)
                      / Adora2a protein, mouse (NLM Chemicals) / MAPT protein,
                      human (NLM Chemicals) / Receptor, Adenosine A2A (NLM
                      Chemicals) / tau Proteins (NLM Chemicals) / Complement C1q
                      (NLM Chemicals)},
      cin          = {AG Halle},
      ddc          = {610},
      cid          = {I:(DE-2719)1013034},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342)},
      pid          = {G:(DE-HGF)POF3-342},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31599329},
      pmc          = {pmc:PMC6821333},
      doi          = {10.1093/brain/awz288},
      url          = {https://pub.dzne.de/record/144978},
}