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Immunohistochemical analysis of ubiquilin‐1 in the human hippocampus: Association with neurofibrillary tangle pathology
Author(s) -
Mizukami Katsuyoshi,
Abrahamson Eric E.,
Mi Zhiping,
Ishikawa Masanori,
Watanabe Kazushi,
Kinoshita Setsuo,
Asada Takashi,
Ikonomovic Milos D.
Publication year - 2014
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1111/neup.12055
Subject(s) - dentate gyrus , nucleoplasm , neuropil , hippocampus , subiculum , pathology , neurofibrillary tangle , biology , hippocampal formation , entorhinal cortex , cytoplasm , alzheimer's disease , neuroscience , microbiology and biotechnology , medicine , senile plaques , central nervous system , nucleolus , disease
This post mortem immunohistochemical study examined the localization and distribution of ubiquilin‐1 ( UBL ), a shuttle protein which interacts with ubiquitin and the proteasome, in the hippocampus from A lzheimer's disease ( AD ) dementia cases, and age‐matched cases without dementia. In B raak stages 0– I – II cases, UBL immunoreactivity was detected in a dense fiber network in the neuropil, and in the cell cytoplasm and nucleoplasm of neurons in Cornu Ammonis ( CA ) fields and dentate gyrus granular neurons. In B raak stages III ‐ IV and V ‐ VI cases, UBL immunoreactivity was reduced in the neuropil and in the cytoplasm of the majority of CA1 neurons; some CA1 pyramidal neurons and the majority of CA2 /3 pyramidal, CA4 multipolar, and dentate granular neurons had markedly increased UBL immunoreactivity in the nucleoplasm. Dual immunofluorescence analysis of UBL and antibody clone AT8 revealed co‐localization most frequently in CA1 pyramidal neurons in B raak stage III ‐ IV and V ‐ VI cases. Further processing using the pan‐amyloid marker X ‐34 revealed prominent UBL / X ‐34 dual labeling of extracellular NFT confined to the CA1 /subiculum in B raak stage V ‐ VI cases. Our results demonstrate that in AD hippocampus, early NFT changes are associated with neuronal up‐regulation of UBL in nucleoplasm, or its translocation from the cytoplasm to the nucleus. The perseverance of UBL changes in CA2 /3, CA4 and dentate gyrus, generally considered as more resistant to NFT pathology, but not in the CA1 , may mark a compensatory, potentially protective response to increased tau phosphorylation in hippocampal neurons; the failure of such a response may contribute to neuronal degeneration in end‐stage AD .