TDP-43 is deposited in the Guam parkinsonism-dementia complex brains

Abstract

TDP-43, a nuclear factor that functions in regulating transcription and alternative splicing, was recently identified as a component of the ubiquitin-positive, tau-negative inclusions specific for frontotemporal lobar degeneration (FTLD-U) and amyotrophic lateral sclerosis (ALS). In the present study, we carried out immunohistochemical and biochemical analyses of brains of Guamanians with the parkinsonism-dementia complex (G-PDC) using anti-TDP-43, anti-tau and anti-ubiquitin antibodies. Immunohistochemistry with anti-TDP-43 antibodies revealed various types of positive structures in the frontotemporal and hippocampal regions of G-PDC cases. Most of these structures were negative for tau. By immunoblot analysis with the TDP-43 antibody, an abnormal 45 kDa band, as well as a diffuse staining throughout the gel, was detected in the sarkosyl-insoluble fractions of G-PDC brains. Dephosphorylation has shown that abnormal phosphorylation takes place in the accumulated TDP-43 seen in FTLD-U and ALS. These results suggest that accumulation of TDP-43 is a common process in certain neurodegenerative disorders, including FTLD-U, ALS and G-PDC.