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J Neuropathol Exp Neurol. 2008 Dec;67(12):1159-65. doi: 10.1097/NEN.0b013e31818e8951.

Colocalization of transactivation-responsive DNA-binding protein 43 and huntingtin in inclusions of Huntington disease.

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Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada.


Transactivation-responsive DNA-binding protein 43 (TDP-43) is a component of pathological inclusions in amyotrophic lateral sclerosis and several forms of sporadic and familial frontotemporal lobar degeneration. Transactivation-responsive DNA-binding protein 43-immunostained inclusions have also been found in other neurodegenerative disorders including Alzheimer disease, dementia with Lewy bodies, and parkinsonism dementia complex of Guam. Here, we analyzed the occurrence of TDP-43 immunostaining in Huntington disease, which is characterized by inclusions containing mutated huntingtin. In all Huntington disease cases studied, TDP-43 was frequently colocalized with huntingtin in dystrophic neurites and various intracellular inclusions, but not in intranuclear inclusions; the latter were only stained with huntingtin and anti-ubiquitin antibodies. Two phosphorylation-dependent TDP-43 antibodies proved to be superior for detecting pathological inclusions because they did not stain nonphosphorylated TDP-43 in normal nuclei; staining of normal nuclei with phosphorylation-independent antibodies obscured the inclusions. Our results further add to the hypothesis that TDP-43 may be involved in the pathology of a variety of neurodegenerative disorders.

[Indexed for MEDLINE]

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