White matter lesions in the brain with frontotemporal lobar degeneration with motor neuron disease: TDP-43-immunopositive inclusions co-localize with p62, but not ubiquitin.
Recently, TDP-43 was established as a major component of the ubiquitinated inclusions found in both amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with motor neuron disease (FTLD-MND). However, differences in the underlying pathogenesis between ALS and FTLD-MND remain yet to be elucidated. Originally, TDP-43-immunopositive inclusions were found in neuronal cells and reported to be ubiquitinated. This study shows that TDP-43-positive inclusions were distributed throughout the subcortical white matter except for the occipital lobe in the FTLD-MND brain, but not in the ALS brain. TDP-43-positive inclusions were also prominent features of pathologically proven FTLD-MND cases (p-FTLD-MND) without history of apparent clinical cognitive decline. A substantial fraction of these inclusions was also p62-immunoreactive, and another noteworthy feature was that those inclusions did not stain positively for ubiquitin. Significant correlations between immunoreactivity for TDP-43 and p62 were observed, particularly in p-FTLD-MND (Pearson correlation coefficient, 0.976). Furthermore, TDP-43 extracted from white matter appeared to be uncleaved. These results indicate that pathological changes might take place within the white matter also in the brain with FTLD-MND, but in a different manner than within the gray matter.
Hiji
Masanori
M
Department of Neurology, Mifukai Viha-ra Hananosato Hospital, Miyoshi, 728-0001, Japan.
Takahashi
Tetsuya
T
Fukuba
Hiromasa
H
Yamashita
Hiroshi
H
Kohriyama
Tatsuo
T
Matsumoto
Masayasu
M
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000368:Aged; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003704:Dementia / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000378:metabolism / Q000473:pathology*; D000071456:Sequestosome-1 Protein; D025801:Ubiquitin / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D025801:Ubiquitin