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

C Schwab, T Arai, M Hasegawa, S Yu… - … of Neuropathology & …, 2008 - academic.oup.com
C Schwab, T Arai, M Hasegawa, S Yu, PL McGeer
Journal of Neuropathology & Experimental Neurology, 2008academic.oup.com
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 …
Abstract
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.
Oxford University Press