Limbic Predominant Age-Related TDP-43 Encephalopathy (LATE): Clinical and Neuropathological Associations

Lilah M. Besser, Merilee A. Teylan, Peter T. Nelson

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


Recently, a consensus working group provided new terminology for a common disease entity, limbic predominant age-related TDP-43 encephalopathy (LATE), and its neuropathological substrate (LATE-NC). LATE-NC not only often co-occurs with Alzheimer disease neuropathological change (ADNC), but also may present in isolation. The present study aimed to investigate potential risk factors and neuropathological characteristics associated with LATE-NC. A sample of 616 autopsied participants (>75 years at death), with TDP-43 immunohistochemical studies performed, was obtained from the National Alzheimer's Coordinating Center. Logistic regression analyses examined associations between demographic, clinical and neuropathological characteristics and LATE-NC (TDP-43 in amygdala, hippocampus, or entorhinal/inferior temporal cortex) (alpha = 0.05). Adjusted models indicated that ADNC, hippocampal sclerosis (HS), arteriolosclerosis, and limbic or amygdala-predominant Lewy body disease (LBD), but not other LBD subtypes, were associated with higher odds of LATE-NC, whereas congestive heart failure (CHF) and motor problems as first predominant symptom were associated with lower odds of LATE-NC. Our findings corroborate previous studies indicating associations between LATE-NC and ADNC, HS, and arteriolosclerosis. Novel findings suggest the association with LATE-NC is restricted to amygdala/limbic-predominant subtype of LBD, and a possible protective (or competing risk) association with CHF. This study may inform future hypothesis-driven research on LATE-NC, a common brain disease of aging.

Original languageEnglish
Pages (from-to)305-313
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Issue number3
StatePublished - Mar 1 2020

Bibliographical note

Publisher Copyright:
© 2019 American Association of Neuropathologists, Inc. All rights reserved.


  • Alzheimer
  • Hippocampus
  • LATE
  • Limbic predominant age related TDP-43 encephalopathy
  • Risk factors
  • TDP-43

ASJC Scopus subject areas

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


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