TDP-43 is associated with a reduced likelihood of rendering a clinical diagnosis of dementia with Lewy bodies in autopsy-confirmed cases of transitional/diffuse Lewy body disease

Marina Buciuc, Jennifer L. Whitwell, Bradley F. Boeve, Tanis J. Ferman, Jonathan Graff-Radford, Rodolfo Savica, Kejal Kantarci, Julie A. Fields, David S. Knopman, Ronald C. Petersen, Joseph E. Parisi, Melissa E. Murray, Dennis W. Dickson, Keith A. Josephs

Research output: Contribution to journalArticle


Background: Trans-active response DNA-binding protein of 43 kDa (TDP-43) can be detected in up to 63% of autopsy-confirmed Lewy body disease (LBD) cases. It is unclear whether TDP-43 is associated with a decreased likelihood of a clinical diagnosis of probable dementia with Lewy bodies (pDLB) during life. Methods: In an autopsy cohort of 395 cognitively impaired patients from the Mayo Clinic Alzheimer’s Disease Research Center, we determined the presence of TDP-43 in the hippocampus [hTDP-43(+)] and examined associations between hTDP-43 and an antemortem pDLB clinical diagnosis with multiple regression analyses. For this study, given our specific question, we only counted transitional and diffuse Lewy body disease as LBD positive (LBD+). Results: One-hundred forty-five cases (37%) were hTDP-43(+) and 156 (39%) were LBD+; co-pathology was noted in 63 (16%) cases. Patients with pDLB− LBD+ were more likely to be older, hTDP-43(+) and have high Braak neurofibrillary tangle (NFT) status compared to the pDLB+ LBD+ patients. After accounting for older age at death and high Braak NFT status, hTDP-43(+) status was associated with the absence of a clinical diagnosis of pDLB despite LBD+ status (p < 0.05). Conclusion: The absence of a diagnosis of pDLB during life in patients with LBD is associated with older age, high Braak NFT stage and hTDP-43, each feature contributing independently to a lower likelihood of a clinical diagnosis of pDLB during life.

Original languageEnglish (US)
Pages (from-to)1444-1453
Number of pages10
JournalJournal of Neurology
Issue number5
StatePublished - May 1 2020



  • Clinical diagnosis
  • Dementia with Lewy bodies
  • Lewy body disease
  • Pathology
  • TDP-43

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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