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@ARTICLE{Briel:155769,
      author       = {Briel, Nils and Pratsch, Katrin and Roeber, Sigrun and
                      Arzberger, Thomas and Herms, Jochen},
      title        = {{C}ontribution of the astrocytic tau pathology to synapse
                      loss in progressive supranuclear palsy and corticobasal
                      degeneration.},
      journal      = {Brain pathology},
      volume       = {31},
      number       = {4},
      issn         = {1750-3639},
      address      = {Oxford},
      publisher    = {Wiley-Blackwell},
      reportid     = {DZNE-2021-00937},
      pages        = {e12914},
      year         = {2021},
      abstract     = {Primary 4-repeat tauopathies with frontotemporal lobar
                      degeneration (FTLD) like Progressive Supranuclear Palsy
                      (PSP) or Corticobasal Degeneration (CBD) show diverse
                      cellular pathology in various brain regions. Besides shared
                      characteristics of neuronal and oligodendroglial cytoplasmic
                      inclusions of accumulated hyperphosphorylated tau protein
                      (pTau), astrocytes in PSP and CBD contain pathognomonic pTau
                      aggregates - hence, lending the designation tufted
                      astrocytes (TA) or astrocytic plaques (AP), respectively.
                      pTau toxicity is most commonly assigned to neurons, whereas
                      the implications of astrocytic pTau for maintaining
                      neurotransmission within the tripartite synapse of human
                      brains is not well understood. We performed
                      immunofluorescent synapse labeling and automated puncta
                      quantification in the medial frontal gyrus (MFG) and
                      striatal regions from PSP and CBD postmortem samples to
                      capture morphometric synaptic alterations. This approach
                      indicated general synaptic losses of both, excitatory and
                      inhibitory bipartite synapses in the frontal cortex of PSP
                      cases, whereas in CBD lower synapse densities were only
                      related to astrocytic plaques. In contrast to tufted
                      astrocytes in PSP, affected astrocytes in CBD could not
                      preserve synaptic integrity within their spatial domains,
                      when compared to non-affected internal astrocytes or
                      astrocytes in healthy controls. These findings suggest a
                      pTau pathology-associated role of astrocytes in maintaining
                      connections within neuronal circuits, considered as the
                      microscopic substrate of cognitive dysfunction in CBD. By
                      contrasting astrocytic-synaptic associations in both
                      diseases, we hereby highlight astrocytic pTau as an
                      important subject of prospective research and as a potential
                      cellular target for therapeutic approaches in the primary
                      tauopathies PSP and CBD.},
      keywords     = {Aged / Aged, 80 and over / Astrocytes: pathology / Brain:
                      pathology / Corticobasal Degeneration: pathology / Female /
                      Frontotemporal Lobar Degeneration: pathology / Humans /
                      Inclusion Bodies: pathology / Male / Middle Aged / Neurons:
                      pathology / Supranuclear Palsy, Progressive: metabolism /
                      Supranuclear Palsy, Progressive: pathology / Tauopathies:
                      pathology / tau Proteins: metabolism / astrocytic plaques
                      (Other) / corticobasal degeneration (Other) / progressive
                      supranuclear palsy (Other) / synapse loss (Other) /
                      tauopathy (Other) / tufted astrocytes (Other)},
      cin          = {AG Herms / Neuropathology / Brainbank},
      ddc          = {610},
      cid          = {I:(DE-2719)1110001 / I:(DE-2719)1140013},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33089580},
      pmc          = {pmc:PMC8412068},
      doi          = {10.1111/bpa.12914},
      url          = {https://pub.dzne.de/record/155769},
}