Appearance pattern of TDP-43 in Japanese frontotemporal lobar degeneration with ubiquitin-positive inclusions.
TAR-DNA-binding protein 43 (TDP-43) was identified as a major component of ubiquitin-positive intracellular inclusions from brains of patients with frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). Here, we immunohistochemically investigated the appearance pattern of TDP-43 to compare the distribution of TDP-43-positive structures with that of ubiquitin-positive structures in brains of seven patients with Japanese FTLD-U, five of atypical Pick's disease (aPiD) and two of dementia with motor neuron disease (D-MND), as well as two patients with PiD as control. TDP-43-immunoreactivity generally colocalized to ubiquitin-immunoreactivity in both neuronal cytoplasmic inclusions and neurites in FTLD-U brains, but TDP-43-immunoreactivity alone or ubiquitin-immunoreactivity alone was also observed. In five aPiD cases, double-immunostaining with TDP-43 and ubiquitin demonstrated that diffuse neuronal cytoplasmic immunostaining for ubiquitin did not always display TDP-43-immunoreactivity. In contrast, ubiquitin-positive neuronal cytoplasmic inclusions usually displayed TDP-43-immunoreactivity in two D-MND cases, although most glial inclusions in one of two cases were immunostained only for TDP-43. TDP-43-positive structures were not detected in two PiD cases. Thus, the ratio in the appearance pattern of TDP-43 and ubiquitin was different between aPiD and D-MND, leading to the hypothesis that this difference may be associated with the two pathogenic variants related to clinical and pathological heterogeneity in FTLD-U.
Higashi
Shinji
S
Department of Psychiatry, Juntendo Tokyo Koto Geriatric Medical Center, Juntendo University School of Medicine, 3-3-20 Shinsuna, Koto-ku, Tokyo 136-0075, Japan. shinji@med.juntendo.ac.jp
Iseki
Eizo
E
Yamamoto
Ryoko
R
Minegishi
Michiko
M
Hino
Hiroaki
H
Fujisawa
Koshiro
K
Togo
Takashi
T
Katsuse
Omi
O
Uchikado
Hirotake
H
Furukawa
Yoshiko
Y
Kosaka
Kenji
K
Arai
Heii
H
D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; 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; D008875:Middle Aged; D025801:Ubiquitin / Q000378:metabolism*
D004268:DNA-Binding Proteins; D025801:Ubiquitin