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Journal of Neurology
Published in: Journal of Neurology 5/2020

01-05-2020 | Autopsy | Original Communication

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

Authors: 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

Published in: Journal of Neurology | Issue 5/2020

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Abstract

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.
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Metadata
Title
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
Authors
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
Publication date
01-05-2020
Publisher
Springer Berlin Heidelberg
Published in
Journal of Neurology / Issue 5/2020
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-020-09718-2

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