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Neuronal intranuclear inclusion disease (NIID) is a rare heterogeneous progressive neurodegenerative disease characterized by the presence of eosinophilic hyaline intranuclear inclusions in neuronal and glial cells of the CNS, peripheral cells of the autonomic nervous system, visceral organs and skin. The clinical presentation is broadly heterogeneous and includes limb weakness, dementia, seizures, ataxia, and parkinsonism. High-intensity signal in the corticomedullary junction on brain MRI is a characteristic finding in NIID. We describe a 65-year-old patient presenting with mild cognitive impairment, evolving in dementia with behavioral disturbances and parkinsonism. Brain MRI showed mild global cortical atrophy, more pronounced in the cingulate and temporal cortex and mild leukoaraiosis, but no high-intensity signal in corticomedullary junction on diffusion weighted imaging. Neuropathological examination showed p62- and optineurin-positive neuronal intranuclear inclusions in the hippocampus and in some subcortical structures. Glial cells did not present any intranuclear inclusions, and no spongiotic changes proximal to the U-fibers or diffuse myelin pallor were disclosed in the white matter. We report on a case with pathological features of NIID showing different neuroimaging and pathological findings. We noted an absence of typical MRI abnormalities, lack of intranuclear inclusions in glial cells, and prominent involvement of hippocampal neurons, refining the clinico-pathological spectrum of the disease.

Mutations in the gene encoding the F-box only protein 7 (FBXO7) cause PARK15, an autosomal recessive form of juvenile parkinsonism. Although the brain pathology in PARK15 patients remains unexplored, in vivo imaging displays severe loss of nigrostriatal dopaminergic terminals. Understanding the pathogenesis of PARK15 might therefore illuminate the mechanisms of the selective dopaminergic neuronal degeneration, which could also be important for understanding idiopathic Parkinson disease (PD). The expression of FBXO7 in the human brain remains poorly characterized, and its expression in idiopathic PD and different neurodegenerative diseases has not been investigated. Here, we studied FBXO7 protein expression in brain samples of normal controls (n = 9) and from patients with PD (n = 13), multiple system atrophy (MSA) (n = 5), Alzheimer disease (AD) (n = 5), and progressive supranuclear palsy (PSP) (n = 5) using immunohistochemistry with 2 anti-FBXO7 antibodies. We detected widespread brain FBXO7 immunoreactivity, with the highest levels in neurons of the cerebral cortex, putamen, and cerebellum. There were no major differences between normal and PD brains overall, but FBXO7 immunoreactivity was detected in large proportions of α-synuclein-positive inclusions (Lewy bodies, Lewy neurites, glial cytoplasmic inclusions), where it colocalized with α-synuclein in PD and MSA cases. By contrast, weak FBXO7 immunoreactivity was occasionally detected in tau-positive inclusions in AD and PSP. These findings suggest a role for FBXO7 in the pathogenesis of the synucleinopathies. Copyright