Incipient intranuclear inclusion body disease in a 78-year-old woman

Abstract

We report an incipient case of intranuclear inclusion body disease (INIBD) in a 78-year-old woman. No apparent neurological symptoms were noticed during the clinical course. Post mortem examination revealed widespread occurrence of eosinophilic intranuclear inclusions in neuronal and glial cells of the central and peripheral nervous systems, as well as in parenchymal cells of the visceral organs. The inclusions were observed more frequently in glial cells than in neuronal cells. Ultrastructurally, the inclusions consisted of granular and filamentous material. Immunohistochemically, the inclusions were positive for ubiquitin, ubiquitin-related proteins (NEDD8 ultimate buster 1, small ubiquitin modifier-1, small ubiquitin modifier-2 and p62), promyelocytic leukemia protein and abnormally expanded polyglutamine. Consistent with previous studies, the vast majority of inclusion-bearing glial cells were astrocytes. Furthermore, p25α-positive oligodendrocytes rarely contained intranuclear inclusions. These findings suggest that INIBD may occur in non-demented elderly individuals and that oligodendrocyte is also involved in the disease process of INIBD.

Ubiquitin‐related proteins in neuronal and glial intranuclear inclusions in intranuclear inclusion body disease

“…Recently, Mori et al . showed that neuronal and glial INI in a case of INIBD were immunopositive for NUB1 10 . In the present study, we demonstrated that NUB1 immunoreactivity was seen in all five cases of INIBD and that NUB1‐positive inclusions relative to the total number of inclusions were 49% in neurons and 19% in glial cells.…”

“…The INI of INIBD are 1‐ to 10‐µm‐sized, spherical hyalinized inclusions consisting of filamentous aggregates 5 . Immunohistochemically, INI in INIBD have been reported to be positive for ubiquitin 8 and ubiquitin‐related proteins (URP), including p62, 10 NUB1, 10 SUMO‐1 2,11,12 and SUMO‐2 10 . They are negative for proteins implicated in the structural elements of abnormal inclusions in neurodegenerative disorders (tau, α‐synuclein, β‐amyloid and neurofilament) 13 .…”

Atypical sporadic CJD‐MM phenotype with white matter kuru plaques associated with intranuclear inclusion body and argyrophilic grain disease

“…We cannot evaluate which symptoms are due to INIBD in our case. However, it must be mentioned that INIBD has been reported in elderly individuals without clinical symptoms, including a case reported in a community‐based study . Immunoreactivity for FUS has been reported for the intranuclear inclusions and also for optineurin .…”

FUS immunoreactivity of neuronal and glial intranuclear inclusions in intranuclear inclusion body disease

“…Immunohistochemically, INIBs in INIBD are positive for ubiquitin and ubiquitin‐related proteins (NUB1, SUMO‐1 and p62) [8,9,23] and a proportion of INIBs are immunolabelled with anti‐polyQ antibody 1C2 [8,9]. Recently, Woulfe et al .…”

“…Consistent with previous reports [5,6,8], INIBs were much more frequent in glial cells (approximately 10%) than in neurones (less than 1%). The vast majority of inclusion‐bearing glial cells are astrocytic and others may be oligodendrocytes [6,9]. Based on these findings, the dysfunction of astrocytes with INIBs may cause secondary damage to both myelin and axons in the cerebral white matter, which is a cardinal neuropathological feature in adult‐onset INIBD [8,9].…”