title: Appearance pattern of TDP-43 in Japanese frontotemporal lobar degeneration with ubiquitin-positive inclusions.
abstract: 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.
authors.affiliation: 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
authors.forename: Shinji
authors.initials: S
authors.lastname: Higashi
authors.forename: Eizo
authors.initials: E
authors.lastname: Iseki
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yamamoto
authors.forename: Michiko
authors.initials: M
authors.lastname: Minegishi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hino
authors.forename: Koshiro
authors.initials: K
authors.lastname: Fujisawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Togo
authors.forename: Omi
authors.initials: O
authors.lastname: Katsuse
authors.forename: Hirotake
authors.initials: H
authors.lastname: Uchikado
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Furukawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Kosaka
authors.forename: Heii
authors.initials: H
authors.lastname: Arai
mesh_terms: 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*
chemical_list: D004268:DNA-Binding Proteins; D025801:Ubiquitin