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

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. LeeJohn Q. Trojanowski

Research output: Contribution to journalArticle

268 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)221-229
Number of pages9
JournalActa Neuropathologica
Volume114
Issue number3
DOIs
StatePublished - Sep 1 2007

Keywords

  • Dementia with Lewy bodies
  • Frontotemporal lobar degeneration
  • Parkinson's disease
  • TDP-43

ASJC Scopus subject areas

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

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    Nakashima-Yasuda, H., Uryu, K., Robinson, J., Xie, S. X., Hurtig, H., Duda, J. E., Arnold, S. E., Siderowf, A., Grossman, M., Leverenz, J. B., Woltjer, R., Lopez, O. L., Hamilton, R., Tsuang, D. W., Galasko, D., Masliah, E., Kaye, J., Clark, C. M., Montine, T. J., ... Trojanowski, J. Q. (2007). Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases. Acta Neuropathologica, 114(3), 221-229. https://doi.org/10.1007/s00401-007-0261-2