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TDP-43 immunoreactivity in anoxic, ischemic and neoplastic lesions of the central nervous system

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Abstract

TDP-43 proteinopathies are a newly categorized group of neurodegenerative diseases characterized by progressive cognitive and motor impairments associated with the abnormal accumulation and mislocalization of the nuclear TAR–DNA-binding protein-43 (TDP-43) in neurons and glia. Little is known about the expression and distribution of TDP-43 in normal and pathologic states. To determine whether TDP-43 inclusions arise in response to metabolic insults such as anoxia or ischemia, a panel of anoxic, ischemic and neoplastic lesions was examined for TDP-43 expression by immunohistochemistry. These lesions did not exhibit TDP-43 inclusions like those seen in neurodegenerative frontotemporal dementia and motor neuron disease. However, TDP-43 was found in Rosenthal fibers and eosinophilic granular bodies associated with low-grade tumors and reactive brain tissue. Furthermore, cytoplasmic TDP-43 was seen in M-phase tumor cells, but not in mitotic spindles. These findings expand our knowledge of the distribution and localization of TDP-43, and indicate that the TDP-43 inclusions seen in frontotemporal dementias and motor neuron diseases are specific to a neurodegenerative process.

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Acknowledgments

Supported by an intradepartmental grant from the Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania (to EBL) and a grant by the Federal Ministry of Education and Research (BMBF: “Degenerative dementias: Target identification, validation and translation into treatment strategies (01GI0704)” to MN).

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, 19104, USA

    Edward B. Lee, Virginia M.-Y. Lee & John Q. Trojanowski

  2. Center for Neuropathology and Prion Research, Ludwig-Maximilians University Munich, Feodor-Lynen-Str. 23, 81377, Munich, Germany

    Manuela Neumann

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  1. Edward B. Lee
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  2. Virginia M.-Y. Lee
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  3. John Q. Trojanowski
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  4. Manuela Neumann
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Correspondence to Manuela Neumann.

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Lee, E.B., Lee, V.MY., Trojanowski, J.Q. et al. TDP-43 immunoreactivity in anoxic, ischemic and neoplastic lesions of the central nervous system. Acta Neuropathol 115, 305–311 (2008). https://doi.org/10.1007/s00401-007-0331-5

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  • DOI: https://doi.org/10.1007/s00401-007-0331-5

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