Astrocyte-vascular interactions are disturbed in cerebral white matter of adult-onset neuronal intranuclear inclusion disease

Abstract Adult-onset neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease that is pathologically characterized by eosinophilic hyaline intranuclear inclusions, mainly in astrocytes, and cerebral white matter degeneration. However, the pathogenesis underlying these neuropathological findings remains unclear. We previously reported an autopsy case of adult-onset NIID with characteristic perivascular findings. In that case, the perivascular areas were preserved despite cerebral white matter damage but dense glial fibrillary acidic protein-immunoreactive astrocytic processes were observed around the blood vessels. The present study examined 2 additional cases and confirmed that the above findings were common in patients with adult-onset NIID. To investigate the underlying pathophysiology behind these findings, immunohistochemistry was performed for proteins located in the astrocytic end-feet. In the cerebral white matter of all NIID cases, there was an altered distribution of aquaporin 4 (AQP4) with increased AQP4-immunopositive areas compared to control cases. These results suggest that the interaction between astrocytes and blood vessels, particularly involving water homeostasis, may be impaired in the cerebral white matter of patients with NIID.