Acta Neuropathologica

, Volume 114, Issue 3, pp 221–229

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. Lee
  • John Q. Trojanowski
Original Paper

DOI: 10.1007/s00401-007-0261-2

Cite this article as:
Nakashima-Yasuda, H., Uryu, K., Robinson, J. et al. Acta Neuropathol (2007) 114: 221. doi:10.1007/s00401-007-0261-2

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.

Keywords

Frontotemporal lobar degenerationTDP-43Dementia with Lewy bodiesParkinson’s disease

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Hanae Nakashima-Yasuda
    • 1
  • Kunihiro Uryu
    • 1
  • John Robinson
    • 1
  • Sharon X. Xie
    • 4
  • Howard Hurtig
    • 3
  • John E. Duda
    • 3
    • 6
  • Steven E. Arnold
    • 5
  • Andrew Siderowf
    • 3
  • Murray Grossman
    • 3
  • James B. Leverenz
    • 7
    • 8
    • 10
    • 11
  • Randy Woltjer
    • 9
  • Oscar L. Lopez
    • 12
  • Ronald Hamilton
    • 13
  • Debby W. Tsuang
    • 7
    • 11
  • Douglas Galasko
    • 14
  • Eliezer Masliah
    • 14
    • 15
  • Jeffrey Kaye
    • 16
  • Christopher M. Clark
    • 3
  • Thomas J. Montine
    • 9
  • Virginia M. -Y. Lee
    • 1
  • John Q. Trojanowski
    • 1
    • 2
  1. 1.Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease ResearchUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  2. 2.Institute on AgingUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  3. 3.Department of NeurologyUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  4. 4.Department of Biostatistics and EpidemiologyUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  5. 5.Department of PsychiatryUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  6. 6.Parkinson’s Disease Research, Education and Clinical CenterPhiladelphia VAMCPhiladelphiaUSA
  7. 7.Department of Psychiatry and Behavioral SciencesUniversity of WashingtonSeattleUSA
  8. 8.Department of NeurologyUniversity of WashingtonSeattleUSA
  9. 9.Department of PathologyUniversity of WashingtonSeattleUSA
  10. 10.Mental Illness Research, Education, and Clinical CenterVA Puget Sound Health Care SystemSeattleUSA
  11. 11.Parkinson’s Disease Research, Education, and Clinical CenterVA Puget Sound Health Care SystemSeattleUSA
  12. 12.Department of NeurologyUniversity of PittsburghPittsburghUSA
  13. 13.Department of PathologyUniversity of PittsburghPittsburghUSA
  14. 14.Department of NeuroscienceUniversity of California-San DiegoSan DiegoUSA
  15. 15.Department of PathologyUniversity of California-San DiegoSan DiegoUSA
  16. 16.Department of NeurologyOregon Health & Sciences UniversityPortlandUSA