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J Neurol. 2020 Jan 31. doi: 10.1007/s00415-020-09718-2. [Epub ahead of print]

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.

Author information

1
Department of Neurology, College of Medicine and Science, Mayo Clinic, 200 First Street S.W., Rochester, MN, 55905, USA.
2
Department of Radiology, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA.
3
Department of Psychiatry (Neuropsychology), Mayo Clinic, 4500 San Pablo Rd S, Jacksonville, FL, 32224, USA.
4
Department of Psychiatry (Neuropsychology), Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA.
5
Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA.
6
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Rd S, Jacksonville, FL, 32224, USA.
7
Department of Neurology, College of Medicine and Science, Mayo Clinic, 200 First Street S.W., Rochester, MN, 55905, USA. josephs.keith@mayo.edu.

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.

KEYWORDS:

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

PMID:
32006160
DOI:
10.1007/s00415-020-09718-2

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