Ubiquilin-1 immunoreactivity is concentrated on Hirano bodies and dystrophic neurites in Alzheimer's disease brains
Article first published online: 28 OCT 2013
© 2013 British Neuropathological Society
Neuropathology and Applied Neurobiology
Volume 39, Issue 7, pages 817–830, December 2013
How to Cite
Satoh, J., Tabunoki, H., Ishida, T., Saito, Y. and Arima, K. (2013), Ubiquilin-1 immunoreactivity is concentrated on Hirano bodies and dystrophic neurites in Alzheimer's disease brains. Neuropathology and Applied Neurobiology, 39: 817–830. doi: 10.1111/nan.12036
- Issue published online: 28 OCT 2013
- Article first published online: 28 OCT 2013
- Accepted manuscript online: 20 FEB 2013 05:38AM EST
- Manuscript Accepted: 7 FEB 2013
- Manuscript Received: 29 AUG 2012
- Research on Intractable Diseases. Grant Numbers: H21-Nanchi-Ippan-201, H22-Nanchi-Ippan-136
- Ministry of Health, Labour and Welfare (MHLW), Japan
- Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. Grant Numbers: S0801043, C22500322
- Alzheimer's disease;
- dystrophic neurites;
- Hirano bodies;
Ubiquilin-1 acts as an adaptor protein that mediates the translocation of polyubiquitinated proteins to the proteasome for degradation. Although previous studies suggested a key role of ubiquilin-1 in the pathogenesis of Alzheimer's disease (AD), a direct relationship between ubiquilin-1 and Hirano bodies in AD brains remains unknown.
By immunohistochemistry, we studied ubiquilin-1 and ubiquilin-2 expression in the frontal cortex and the hippocampus of six AD and 13 control cases.
Numerous Hirano bodies, accumulated in the hippocampal CA1 region of AD brains, expressed intense immunoreactivity for ubiquilin-1. They were much less frequently found in control brains. However, Hirano bodies did not express a panel of markers for proteasome, autophagosome or pathogenic proteins, such as ubiquilin-2, ubiquitin, p62, LC3, beclin-1, HDAC6, paired helical filament (PHF)-tau, protein-disulphide isomerase (PDI) and phosphorylated TDP-43, but some of them expressed C9orf72. Ubiquilin-1-immunoreactive deposits were classified into four distinct morphologies, such as rod-shaped structures characteristic of Hirano bodies, dystrophic neurites contacting senile plaques, fragmented structures accumulated in the lesions affected with severe neuronal loss, and thread-shaped structures located mainly in the molecular layer of the hippocampus.
Ubiquilin-1 immunoreactivity is concentrated on Hirano bodies and dystrophic neurites in AD brains, suggesting that aberrant expression of ubiquilin-1 serves as one of pathological hallmarks of AD.