Acta Neuropathologica

, Volume 114, Issue 3, pp 221–229

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

Authors

  • Hanae Nakashima-Yasuda
    • Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease ResearchUniversity of Pennsylvania School of Medicine
  • Kunihiro Uryu
    • Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease ResearchUniversity of Pennsylvania School of Medicine
  • John Robinson
    • Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease ResearchUniversity of Pennsylvania School of Medicine
  • Sharon X. Xie
    • Department of Biostatistics and EpidemiologyUniversity of Pennsylvania School of Medicine
  • Howard Hurtig
    • Department of NeurologyUniversity of Pennsylvania School of Medicine
  • John E. Duda
    • Department of NeurologyUniversity of Pennsylvania School of Medicine
    • Parkinson’s Disease Research, Education and Clinical CenterPhiladelphia VAMC
  • Steven E. Arnold
    • Department of PsychiatryUniversity of Pennsylvania School of Medicine
  • Andrew Siderowf
    • Department of NeurologyUniversity of Pennsylvania School of Medicine
  • Murray Grossman
    • Department of NeurologyUniversity of Pennsylvania School of Medicine
  • James B. Leverenz
    • Department of Psychiatry and Behavioral SciencesUniversity of Washington
    • Department of NeurologyUniversity of Washington
    • Mental Illness Research, Education, and Clinical CenterVA Puget Sound Health Care System
    • Parkinson’s Disease Research, Education, and Clinical CenterVA Puget Sound Health Care System
  • Randy Woltjer
    • Department of PathologyUniversity of Washington
  • Oscar L. Lopez
    • Department of NeurologyUniversity of Pittsburgh
  • Ronald Hamilton
    • Department of PathologyUniversity of Pittsburgh
  • Debby W. Tsuang
    • Department of Psychiatry and Behavioral SciencesUniversity of Washington
    • Parkinson’s Disease Research, Education, and Clinical CenterVA Puget Sound Health Care System
  • Douglas Galasko
    • Department of NeuroscienceUniversity of California-San Diego
  • Eliezer Masliah
    • Department of NeuroscienceUniversity of California-San Diego
    • Department of PathologyUniversity of California-San Diego
  • Jeffrey Kaye
    • Department of NeurologyOregon Health & Sciences University
  • Christopher M. Clark
    • Department of NeurologyUniversity of Pennsylvania School of Medicine
  • Thomas J. Montine
    • Department of PathologyUniversity of Washington
  • Virginia M. -Y. Lee
    • Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease ResearchUniversity of Pennsylvania School of Medicine
    • Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease ResearchUniversity of Pennsylvania School of Medicine
    • Institute on AgingUniversity of Pennsylvania School of Medicine
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