Relationship between Bunina bodies and TDP-43 inclusions in spinal anterior horn in amyotrophic lateral sclerosis.

ABSTRACT

AIMS: Amyotrophic lateral sclerosis (ALS) is characterized by upper and lower motor neurone involvement with Bunina bodies (BBs) and TDP-43 inclusions. To elucidate the relationship between BBs and TDP-43 inclusions, we examined the spinal cord from 18 patients with ALS. METHODS: Five serial sections from lumbar cord were first stained with haematoxylin and eosin to detect BBs and subsequently immunostained with anti-TDP-43 antibody. Immunoelectron microscopy was performed on vibratome sections from two cases of ALS. RESULTS: BBs were found in 15 out of 18 cases. TDP-43 inclusions were found in all the cases. The average incidence of anterior horn cells with BBs and TDP-43 inclusions relative to the total number of neurones was 17.1% and 46.4%, respectively. The concurrence of both inclusions in the same neurones was found in 15 cases. The incidence of co-localization of BBs and TDP-43 inclusions was 15.7% of total neurones. The frequency of TDP-43 inclusions was significantly higher in neurones with BBs than in those without. Ultrastructurally, TDP-43-immunoreactive filamentous structures were intermingled with early-stage BBs, but not associated with advanced-stage BBs. CONCLUSION: These findings suggest that there is a close relationship in the occurrence between BBs and TDP-43 inclusions.