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Various heterogeneous nuclear ribonucleoproteins (hnRNPs) are deposited in pathological inclusions of amyotrophic lateral sclerosis (ALS) and related diseases, such as frontotemporal lobar degeneration (FTLD). Recently, poly (rC)-binding protein 2 (PCBP2, hnRNP-E2), a member of the hnRNP family, was reported to be colocalized with transactivation-responsive DNA-binding protein 43 kDa (TDP-43)-immunopositive inclusions in cases of FTLD-TDP. Here, we used immunohistochemical methods to investigate PCBP1 and PCBP2 expression in the spinal cords of sporadic ALS patients, with special reference to TDP-43-positive inclusions. Thirty autopsy cases of sporadic ALS were examined by immunohistochemistry using antibodies against PCBP1, PCBP2, sequestosome 1 (p62), and TDP-43. In control subjects without neurological disorders, neurons predominantly expressed PCBP2, rather than PCBP1, in their cytoplasm and nuclei. Anterior horn cells of sporadic ALS patients often had various levels of PCBP2 expression, and motor neurons with skein-like inclusions often had reduced or lost cytoplasmic and nuclear PCBP2 staining. Notably, one case with FTLD-TDP subtype B pathology had marked colocalization of TDP-43 and PCBP2 in the cytoplasmic inclusions and dystrophic neurites of the cerebral cortex, hippocampus, and spinal cord. In conclusion, PCBP2 was reduced in anterior horn cells of sporadic ALS, but its occurrence in TDP-43 inclusions was a rare phenomenon.

PCBP2 Is Downregulated in Degenerating Neurons and Rarely Observed in TDP-43-Positive Inclusions in Sporadic Amyotrophic Lateral Sclerosis