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@ARTICLE{Lohmann:141488,
      author       = {Lohmann, Stephanie and Bernis, Maria E and Babila, Julius
                      Tachu and Ziemski, Alexandra and Grigoletto, Jessica and
                      Tamgüney, Gültekin},
      title        = {{O}ral and intravenous transmission of α-synuclein fibrils
                      to mice.},
      journal      = {Acta neuropathologica},
      volume       = {138},
      number       = {4},
      issn         = {0001-6322},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DZNE-2020-07812},
      pages        = {515-533},
      year         = {2019},
      abstract     = {Parkinson's disease and related disorders are
                      neuropathologically characterized by cellular deposits of
                      misfolded and aggregated α-synuclein in the CNS.
                      Disease-associated α-synuclein adopts a conformation that
                      causes it to form oligomers and fibrils, which have reduced
                      solubility, become hyperphosphorylated, and contribute to
                      the spatiotemporal spreading of pathology in the CNS. The
                      infectious properties of disease-associated α-synuclein,
                      e.g., by which peripheral route and with which efficiency it
                      can be transmitted, are not fully understood. Here, we
                      investigated the potential of α-synuclein fibrils to induce
                      neurological disease in TgM83+/- mice expressing the A53T
                      mutant of human α-synuclein after oral or intravenous
                      challenge and compared it to intraperitoneal and
                      intracerebral challenge. Oral challenge with 50 µg of
                      α-synuclein fibrils caused neurological disease in two out
                      of eight mice in 220 days and 350 days, and challenge with
                      500 µg in four out of eight mice in 384 ± 131 days,
                      respectively. Intravenous challenge with 50 µg of
                      α-synuclein fibrils led to disease in 208 ± 20 days
                      in 10 out of 10 mice and was in duration comparable to
                      intraperitoneal challenge with 50 µg of α-synuclein
                      fibrils, which caused disease in 10 out of 10 mice in
                      202 ± 35 days. Ten out of 10 mice that were each
                      intracerebrally challenged with 10 µg or 50 µg of
                      α-synuclein fibrils developed disease in
                      156 ± 20 days and 133 ± 4 days, respectively.
                      The CNS of diseased mice displayed aggregates of
                      sarkosyl-insoluble and phosphorylated α-synuclein, which
                      colocalized with ubiquitin and p62 and were accompanied by
                      gliosis indicative of neuroinflammation. In contrast, none
                      of the control mice that were challenged with bovine serum
                      albumin via the same routes developed any neurological
                      disease or neuropathology. These findings are important,
                      because they show that α-synuclein fibrils can neuroinvade
                      the CNS after a single oral or intravenous challenge and
                      cause neuropathology and disease.},
      keywords     = {Administration, Intravenous / Administration, Oral /
                      Animals / Brain: drug effects / Brain: pathology / Disease
                      Models, Animal / Mice / Phosphorylation / Synucleinopathies:
                      chemically induced / Synucleinopathies: pathology /
                      alpha-Synuclein: administration $\&$ dosage /
                      alpha-Synuclein: metabolism},
      cin          = {AG Tamgüney 2},
      ddc          = {610},
      cid          = {I:(DE-2719)1013022},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342)},
      pid          = {G:(DE-HGF)POF3-342},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31230104},
      pmc          = {pmc:PMC6778172},
      doi          = {10.1007/s00401-019-02037-5},
      url          = {https://pub.dzne.de/record/141488},
}