Ubiquitin and ubiquitin-related proteins in the brains of patients with atypical Pick's disease without Pick bodies and dementia with motor neuron disease.

Nine cases of atypical Pick's disease without Pick bodies (aPiD) and seven cases of dementia with motor neuron diseases (D-MND) were compared using immunohistochemistry of ubiquitin (ub) and ub-related proteins. All cases showed rostral-dominant atrophy in the temporal and frontal lobes, although the degree of atrophy with neuronal loss was much more severe in the aPiD cases. In both aPiD and D-MND cases, ub-positive and tau-negative structures were found mainly in the hippocampal dentate gyrus and cerebral cortex. Granular cells of the dentate gyrus showed similar ub-positive intraneuronal inclusions in both cases. In the aPiD cases, most of the ub-positive cortical structures were ub-positive dendrites in layers II-IIIab and layers V-VI, although some neurons also showed diffuse ub-positive staining in the cytoplasm. In the D-MND cases, some neurons showed ub-positive inclusions in layers II-IIIab, and ub-positive dendrites were unremarkable. The number of ub-positive neurons and dendrites in relation to the degree of neuronal loss in the cerebral cortex were then evaluated. The number of ub-positive neurons in the regions showing very mild to mild neuronal loss was significantly greater in the D-MND cases than in the aPiD cases. However, in the aPiD cases, the number of ub-positive neurons was significantly greater in the regions showing moderate neuronal loss. When double-immunostained, almost all ub-positive structures were positive for ub-binding protein p62. Some ub-positive or negative neurons in the cerebral cortex were immunostained with anti-ub ligase (Parkin) and anti-ub C-terminal hydrolase (UCH-L1) antibodies. Granular cells of the dentate gyrus were weakly positive for UCH-L1. There could be some differences in the mechanism by which neurons in the cerebral cortex accumulate ub between aPiD and D-MND.