TDP-43 is deposited in the Guam parkinsonism-dementia complex brains.
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.
Hasegawa
Masato
M
Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan. masato@prit.go.jp
Arai
Tetsuaki
T
Akiyama
Haruhiko
H
Nonaka
Takashi
T
Mori
Hiroshi
H
Hashimoto
Tomoyo
T
Yamazaki
Mineo
M
Oyanagi
Kiyomitsu
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D001923:Brain Chemistry; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000032:analysis*; D005260:Female; D005625:Frontal Lobe / Q000737:chemistry; D006624:Hippocampus / Q000737:chemistry; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020774:Pick Disease of the Brain / Q000378:metabolism; D013702:Temporal Lobe / Q000737:chemistry; D025801:Ubiquitin / Q000032:analysis; D016875:tau Proteins / Q000032:analysis
D004268:DNA-Binding Proteins; C054369:MAPT protein, human; D025801:Ubiquitin; D016875:tau Proteins