TDP‐43 immunoreactivity in anoxic, ischemic and proliferating lesion of the central nervous system

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) protein in neurons and glia. Little is known about the expression and distribution of TDP‐43 in normal and pathologic states. A panel of clinical neuropathologic specimens was examined for TDP‐43 expression by immunohistochemistry. TDP‐43 inclusions like those seen in neurodegenerative frontotemporal dementia and motor neuron disease were not seen in a variety of anoxic, ischemic and proliferating lesions. 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 in pathologic specimens, and indicate that the TDP‐43 inclusions seen in frontotemporal dementias and motor neuron diseases are specific to a neurodegenerative process.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” to MN).