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01-09-2007 | Original Paper

Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases

Authors: Hanae Nakashima-Yasuda, Kunihiro Uryu, John Robinson, Sharon X. Xie, Howard Hurtig, John E. Duda, Steven E. Arnold, Andrew Siderowf, Murray Grossman, James B. Leverenz, Randy Woltjer, Oscar L. Lopez, Ronald Hamilton, Debby W. Tsuang, Douglas Galasko, Eliezer Masliah, Jeffrey Kaye, Christopher M. Clark, Thomas J. Montine, Virginia M. -Y. Lee, John Q. Trojanowski

Published in: Acta Neuropathologica | Issue 3/2007

Abstract

Here, we investigated if TAR-DNA-binding protein-43 (TDP-43), the disease protein in frontotemporal lobar degeneration and ubiquitin inclusions with or without motor neuron disease as well as amyotrophic lateral sclerosis, also formed inclusions in Lewy body (LB) disorders including Parkinson’s disease (PD) without or with dementia (PDD), and dementia with LBs (DLB) alone or in association with Alzheimer’s disease (AD). Immunohistochemical analyses of TDP-43 in clinically well characterized and pathologically confirmed cases of DLB + AD, PD and PDD demonstrated TDP-43 pathology in the following percentage of cases: DLB + AD = 25/80 (31.3%); PD = 5/69 (7.2%); PDD = 4/21 (19%), while DLB and normal controls exhibited no (0/10, 0%) and one cases (1/33, 3%) presenting TDP-43 pathology, respectively. Significant differences in the prevalence of TDP-43 lesions were noted between disease versus normal brains (P < 0.001) as well as demented versus non-demented brains (P < 0.001). Statistical analyses revealed a positive relationship between TDP-43 lesions and several clinical and pathological parameters in these disorders suggesting the TDP-43 pathology may have co-morbid effects in LB diseases. This study expands the concept of TDP-43 proteinopathies by implicating TDP-43 lesions in mechanisms of neurodegeneration in LB disorders.

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Title: Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases
Authors: Hanae Nakashima-Yasuda
Kunihiro Uryu
John Robinson
Sharon X. Xie
Howard Hurtig
John E. Duda
Steven E. Arnold
Andrew Siderowf
Murray Grossman
James B. Leverenz
Randy Woltjer
Oscar L. Lopez
Ronald Hamilton
Debby W. Tsuang
Douglas Galasko
Eliezer Masliah
Jeffrey Kaye
Christopher M. Clark
Thomas J. Montine
Virginia M. -Y. Lee
John Q. Trojanowski
Publication date: 01-09-2007
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 3/2007
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-007-0261-2

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Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases

Abstract

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Abstract

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