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Neuropathol Appl Neurobiol. 2013 Dec;39(7):817-30. doi: 10.1111/nan.12036.

Ubiquilin-1 immunoreactivity is concentrated on Hirano bodies and dystrophic neurites in Alzheimer's disease brains.

Author information

1
Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Tokyo, Japan.

Abstract

AIMS:

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.

METHODS:

By immunohistochemistry, we studied ubiquilin-1 and ubiquilin-2 expression in the frontal cortex and the hippocampus of six AD and 13 control cases.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

Alzheimer's disease; C9orf72; Hirano bodies; aggresomes; dystrophic neurites; ubiquilin-1

PMID:
23421764
DOI:
10.1111/nan.12036
[Indexed for MEDLINE]

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