Ubiquitin and ubiquitin-related proteins in neurons and dendrites of brains of atypical Pick's disease without Pick bodies.
Nine cases of atypical Pick's disease without Pick bodies were investigated immunohistochemically. Ubiquitin (ub)-positive and tau-negative structures were mainly found in the cerebral cortex and hippocampal dentate gyrus. In the cerebral cortex, most of the ub-positive structures had ub-positive dendrites in the neuropil, although some also showed diffuse ub-positive staining in the neuronal cytoplasm. These ub-positive structures were distributed throughout layers II-IIIab and layers V-VI. Granular cells of the dentate gyrus had ub-positive intraneuronal inclusions. When the numbers of ub-positive neurons and dendrites were evaluated in relation to the degree of neuronal loss in the cerebral cortex, the number of ub-positive neurons was significantly lower in regions showing very mild neuronal loss and higher in regions showing moderate neuronal loss. In contrast, ub-positive dendrites were detected even in cortical regions showing very mild neuronal loss. Immunoelectron-microscopically, ub-positive structures contained ub-positive ribosome-like granular components in the neuronal cytoplasm and dendrites, which were occasionally related to the rough endoplasmic reticulum and accompanied by a few filamentous components. Almost all ub-positive structures were positive for ub-binding protein p62 in double-immunostaining method. Some ub-positive or negative neurons in the cerebral cortex were positively immunolabeled with anti-ub ligase (Parkin) and anti-ub C-terminal hydrolase antibodies, whereas dendrites were not labeled by these antibodies. From the present study, it is suggested that in the cerebral cortex, these ubiquitinated proteins may firstly accumulate in the dendrites at the onset of neuronal degeneration, then appear in the neuronal cytoplasm before finally disappearing with neuronal loss.
Furukawa
Yoshiko
Y
Department of Psychiatry, Yokohama City University School of Medicine, Kanazawa-ku, Yokohama, Japan.
Iseki
Eizo
E
Hino
Hiroaki
H
Kanai
Akiko
A
Odawara
Toshinari
T
Kosaka
Kenji
K
D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology; D002540:Cerebral Cortex / Q000737:chemistry / Q000473:pathology; D003712:Dendrites / Q000737:chemistry* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000737:chemistry* / Q000473:pathology; D020774:Pick Disease of the Brain / Q000473:pathology*; D025801:Ubiquitin / Q000032:analysis* / Q000096:biosynthesis; D044767:Ubiquitin-Protein Ligases / Q000032:analysis
D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein