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@ARTICLE{Lohmann:863758,
      author       = {Lohmann, Stephanie and Bernis, Maria E. and Tachu, Babila
                      J. 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         = {1432-0533},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {FZJ-2019-03756},
      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.},
      cin          = {ICS-6},
      ddc          = {610},
      cid          = {I:(DE-Juel1)ICS-6-20110106},
      pnm          = {553 - Physical Basis of Diseases (POF3-553)},
      pid          = {G:(DE-HGF)POF3-553},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31230104},
      UT           = {WOS:000488931000003},
      doi          = {10.1007/s00401-019-02037-5},
      url          = {https://juser.fz-juelich.de/record/863758},
}