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@ARTICLE{Attems:154752,
      author       = {Attems, Johannes and Toledo, Jon B. and Walker, Lauren and
                      Gelpi, Ellen and Gentleman, Steve and Halliday, Glenda and
                      Hortobagyi, Tibor and Jellinger, Kurt and Kovacs, Gabor G.
                      and Lee, Edward B. and Love, Seth and McAleese, Kirsty E.
                      and Nelson, Peter T. and Neumann, Manuela and Parkkinen,
                      Laura and Polvikoski, Tuomo and Sikorska, Beata and Smith,
                      Colin and Grinberg, Lea Tenenholz and Thal, Dietmar R. and
                      Trojanowski, John Q. and McKeith, Ian G.},
      title        = {{N}europathological consensus criteria for the evaluation
                      of {L}ewy pathology in post-mortem brains: a multi-centre
                      study},
      journal      = {Acta neuropathologica},
      volume       = {141},
      number       = {2},
      issn         = {1432-0533},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DZNE-2021-00342},
      pages        = {159 - 172},
      year         = {2021},
      abstract     = {Currently, the neuropathological diagnosis of Lewy body
                      disease (LBD) may be stated according to several staging
                      systems, which include the Braak Lewy body stages (Braak),
                      the consensus criteria by McKeith and colleagues (McKeith),
                      the modified McKeith system by Leverenz and colleagues
                      (Leverenz), and the Unified Staging System by Beach and
                      colleagues (Beach). All of these systems use
                      semi-quantitative scoring (4- or 5-tier scales) of Lewy
                      pathology (LP; i.e., Lewy bodies and Lewy neurites) in
                      defined cortical and subcortical areas. While these systems
                      are widely used, some suffer from low inter-rater
                      reliability and/or an inability to unequivocally classify
                      all cases with LP. To address these limitations, we devised
                      a new system, the LP consensus criteria (LPC), which is
                      based on the McKeith system, but applies a dichotomous
                      approach for the scoring of LP (i.e., "absent" vs.
                      "present") and includes amygdala-predominant and
                      olfactory-only stages. α-Synuclein-stained slides from
                      brainstem, limbic system, neocortex, and olfactory bulb from
                      a total of 34 cases with LP provided by the Newcastle Brain
                      Tissue Resource (NBTR) and the University of Pennsylvania
                      brain bank (UPBB) were scanned and assessed by 16 raters,
                      who provided diagnostic categories for each case according
                      to Braak, McKeith, Leverenz, Beach, and LPC systems. In
                      addition, using LP scores available from neuropathological
                      reports of LP cases from UPBB (n = 202) and NBTR (n = 134),
                      JT (UPBB) and JA (NBTR) assigned categories according to all
                      staging systems to these cases. McKeith, Leverenz, and LPC
                      systems reached good (Krippendorff's α ≈ 0.6), while both
                      Braak and Beach systems had lower (Krippendorff's α ≈
                      0.4) inter-rater reliability, respectively. Using the LPC
                      system, all cases could be unequivocally classified by the
                      majority of raters, which was also seen for $97.1\%$ when
                      the Beach system was used. However, a considerable
                      proportion of cases could not be classified when using
                      Leverenz $(11.8\%),$ McKeith $(26.5\%),$ or Braak $(29.4\%)$
                      systems. The category of neocortical LP according to the LPC
                      system was associated with a 5.9 OR (p < 0.0001) of dementia
                      in the 134 NBTR cases and a 3.14 OR (p = 0.0001) in the 202
                      UPBB cases. We established that the LPC system has good
                      reproducibility and allows classification of all cases into
                      distinct categories. We expect that it will be reliable and
                      useful in routine diagnostic practice and, therefore,
                      suggest that it should be the standard future approach for
                      the basic post-mortem evaluation of LP.},
      keywords     = {Autopsy / Brain: pathology / Brain Mapping / Consensus /
                      Humans / Lewy Bodies: pathology / Lewy Body Disease:
                      classification / Lewy Body Disease: diagnosis / Lewy Body
                      Disease: pathology / Observer Variation / Reproducibility of
                      Results},
      cin          = {AG Neumann},
      ddc          = {610},
      cid          = {I:(DE-2719)1210003},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33399945},
      pubmed       = {33399945},
      pmc          = {pmc:PMC7847437},
      doi          = {10.1007/s00401-020-02255-2},
      url          = {https://pub.dzne.de/record/154752},
}