Neuropathological consensus criteria for the evaluation of Lewy pathology in post-mortem brains: a multi-centre study

Johannes Attems, Jon B. Toledo, Lauren Walker, Ellen Gelpi, Steve Gentleman, Glenda Halliday, Tibor Hortobagyi, Kurt Jellinger, Gabor G. Kovacs, Edward B. Lee, Seth Love, Kirsty E. McAleese, Peter T. Nelson, Manuela Neumann, Laura Parkkinen, Tuomo Polvikoski, Beata Sikorska, Colin Smith, Lea Tenenholz Grinberg, Dietmar R. ThalJohn Q. Trojanowski, Ian G. McKeith

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


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.

Original languageEnglish
Pages (from-to)159-172
Number of pages14
JournalActa Neuropathologica
Issue number2
StatePublished - Feb 2021

Bibliographical note

Funding Information:
JBT is supported by the Edmond J. Safra Fellowship in Movement Disorders.

Funding Information:
JBT is supported by the Edmond J. Safra Fellowship in Movement Disorders. Tissue for this study was provided by the Newcastle Brain Tissue Resource, which is funded in part by a grant from the UK Medical Research Council (G0400074), by Brains for Dementia research, a joint venture between Alzheimer?s Society and Alzheimer?s Research UK and by the NIHR Newcastle Biomedical Research Centre awarded to the Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. This study was supported by a Pump-priming grant from the Alzheimer?s Research UK (ARUK) Newcastle Network Centre. LTG is supported by NIH K24AG053435 and U54 NS100717. The University of Pennsylvania brain bank was supported by NIH P30AG10124 and U19AG062418. GGK is supported by the Rossy Foundation and the Edmond J. Safra Foundation.?TH is supported by the Hungarian Brain Research Program (2017-1.2.1-NKP-2017-00002) and Scientific Research Fund (OTKA-NKFIH-SNN 132999).

Publisher Copyright:
© 2021, The Author(s).


  • Diagnostic neuropathology
  • Lewy body disease

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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