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LATE-NC staging in routine neuropathologic diagnosis: an update

Lookup NU author(s): Professor Johannes Attems, Kirsty McAleese



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2022, The Author(s).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.

Publication metadata

Author(s): Nelson PT, Lee EB, Cykowski MD, Alafuzoff I, Arfanakis K, Attems J, Brayne C, Corrada MM, Dugger BN, Flanagan ME, Ghetti B, Grinberg LT, Grossman M, Grothe MJ, Halliday GM, Hasegawa M, Hokkanen SRK, Hunter S, Jellinger K, Kawas CH, Keene CD, Kouri N, Kovacs GG, Leverenz JB, Latimer CS, Mackenzie IR, Mao Q, McAleese KE, Merrick R, Montine TJ, Murray ME, Myllykangas L, Nag S, Neltner JH, Newell KL, Rissman RA, Saito Y, Sajjadi SA, Schwetye KE, Teich AF, Thal DR, Tome SO, Troncoso JC, Wang S-HJ, White CL, Wisniewski T, Yang H-S, Schneider JA, Dickson DW, Neumann M

Publication type: Article

Publication status: Published

Journal: Acta Neuropathologica

Year: 2023

Volume: 145

Pages: 159–173

Print publication date: 01/02/2023

Online publication date: 13/12/2022

Acceptance date: 22/11/2022

Date deposited: 05/01/2023

ISSN (print): 0001-6322

ISSN (electronic): 1432-0533

Publisher: Springer Science and Business Media Deutschland GmbH


DOI: 10.1007/s00401-022-02524-2

PubMed id: 36512061


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