TDP-43 immunoreactivity in anoxic, ischemic and neoplastic lesions of the central nervous system
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.
KeywordsTDP-43 Ischemia Anoxia Rosenthal fiber Eosinophilic granular body Mitosis Hippocampal sclerosis
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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