LATE-NC staging in routine neuropathologic diagnosis: an update

Peter T. Nelson, Edward B. Lee, Matthew D. Cykowski, Irina Alafuzoff, Konstantinos Arfanakis, Johannes Attems, Carol Brayne, Maria M. Corrada, Brittany N. Dugger, Margaret E. Flanagan, Bernardino Ghetti, Lea T. Grinberg, Murray Grossman, Michel J. Grothe, Glenda M. Halliday, Masato Hasegawa, Suvi R.K. Hokkanen, Sally Hunter, Kurt Jellinger, Claudia H. KawasC. Dirk Keene, Naomi Kouri, Gabor G. Kovacs, James B. Leverenz, Caitlin S. Latimer, Ian R. Mackenzie, Qinwen Mao, Kirsty E. McAleese, Richard Merrick, Thomas J. Montine, Melissa E. Murray, Liisa Myllykangas, Sukriti Nag, Janna H. Neltner, Kathy L. Newell, Robert A. Rissman, Yuko Saito, S. Ahmad Sajjadi, Katherine E. Schwetye, Andrew F. Teich, Dietmar R. Thal, Sandra O. Tomé, Juan C. Troncoso, Shih Hsiu J. Wang, Charles L. White, Thomas Wisniewski, Hyun Sik Yang, Julie A. Schneider, Dennis W. Dickson, Manuela Neumann

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


An international consensus report in 2019 recommended a classification system for limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC). The suggested neuropathologic staging system and nomenclature have proven useful for autopsy practice and dementia research. However, some issues remain unresolved, such as cases with unusual features that do not fit with current diagnostic categories. The goal of this report is to update the neuropathologic criteria for the diagnosis and staging of LATE-NC, based primarily on published data. We provide practical suggestions about how to integrate available genetic information and comorbid pathologies [e.g., Alzheimer’s disease neuropathologic changes (ADNC) and Lewy body disease]. We also describe recent research findings that have enabled more precise guidance on how to differentiate LATE-NC from other subtypes of TDP-43 pathology [e.g., frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS)], and how to render diagnoses in unusual situations in which TDP-43 pathology does not follow the staging scheme proposed in 2019. Specific recommendations are also made on when not to apply this diagnostic term based on current knowledge. Neuroanatomical regions of interest in LATE-NC are described in detail and the implications for TDP-43 immunohistochemical results are specified more precisely. We also highlight questions that remain unresolved and areas needing additional study. In summary, the current work lays out a number of recommendations to improve the precision of LATE-NC staging based on published reports and diagnostic experience.

Original languageEnglish (US)
Pages (from-to)159-173
Number of pages15
JournalActa Neuropathologica
Issue number2
StatePublished - Feb 2023


  • Aging
  • Dementia
  • FTD
  • Hippocampal sclerosis
  • NCI
  • Neuroanatomy
  • Processes
  • Stages
  • TDP-43
  • Humans
  • Frontotemporal Dementia/pathology
  • Amyotrophic Lateral Sclerosis/pathology
  • DNA-Binding Proteins/genetics
  • Alzheimer Disease/pathology

ASJC Scopus subject areas

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


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