PML Nuclear Bodies Are Altered in Adult-Onset Neuronal Intranuclear Hyaline Inclusion Disease.

Neuronal intranuclear hyaline inclusion disease (NIHID) is a neurodegenerative disorder characterized by the presence of eosinophilic nuclear inclusions (NIs) in diverse cell lines in systemic organs. Adult-onset NIHID typically manifests with dementia associated with leukoencephalopathy. The detection of NIs in skin biopsies is useful for an antemortem diagnosis. A previous analysis suggested that NIs in NIHID originated from nuclear bodies (NBs), an important nuclear domain related to the ubiquitin-p62-mediated protein degradation system. In this study, we analyzed skin samples from 5 NIHID and 5 control cases immunohistochemically and electron microscopically. In the control cases, small but significant amounts of ubiquitin- and p62-positive intranuclear structures were found. These structures were consistently colocalized with promyelocytic leukemia protein (PML), an essential component of NBs, in particular when activated. The p62- and PML-positive structures were more frequently found in NIHID cases. Activated NBs, having a core and a shell, were observed by electron microscopy in control but not in NIHID cases. Instead, immature and mature filamentous NIs were found only in the NIHID cases. Our results indicate that NBs could not be normally activated in the NIHID, and an abnormal alteration of NBs might be related to the pathogenesis of NIHID.