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.