Performance of a condensed protocol to assess limbic-predominant age-related TDP-43 encephalopathy neuropathologic change

Heather Maioli, Rhonda Mittenzwei, Jane B. Shofer, Kathryn P. Scherpelz, Desiree Marshall, Amber L. Nolan, Peter T. Nelson, C. Dirk Keene, Caitlin S. Latimer

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is a dementia-related proteinopathy common in the elderly population. LATE-NC stages 2 or 3 are consistently associated with cognitive impairment. A condensed protocol (CP) for the assessment of Alzheimer disease neuropathologic change and other disorders associated with cognitive impairment, recommended sampling of small brain portions from specific neuroanatomic regions that were consolidated, resulting in significant cost reduction. Formal evaluation of the CP for LATE-NC staging was not previously performed. Here, we determined the ability of the CP to identify LATE-NC stages 2 or 3. Forty brains donated to the University of Washington BioRepository and Integrated Neuropathology laboratory with known LATE-NC status were resampled. Slides containing brain regions required for LATE-NC staging were immunostained for phospho-TDP-43 and reviewed by 6 neuropathologists blinded to original LATE-NC diagnosis. Overall group performance distinguishing between LATE-NC stages 0-1 and 2-3 was 85% (confidence interval [CI]: 75%-92%). We also used the CP to evaluate LATE-NC in a hospital autopsy cohort, in which LATE-NC was more common in individuals with a history of cognitive impairment, older age, and/or comorbid hippocampal sclerosis. This study shows that the CP can effectively discriminate higher stages of LATE-NC from low or no LATE-NC and that it can be successfully applied in clinical practice using a single tissue block and immunostain.

Original languageEnglish
Pages (from-to)611-619
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Volume82
Issue number7
DOIs
StatePublished - Jul 1 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s).

Keywords

  • Condensed protocol
  • LATE
  • LATE-NC
  • Limbic predominant age-related TDP-43 encephalopathy neuropathologic change

ASJC Scopus subject areas

  • General Medicine

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