Neuronal Intranuclear Inclusions in Neostriatal Striosomes and Matrix in Huntington’s Disease
Neuronal intranuclear inclusions have recently been described in the cerebral cortex and neostriatum in Huntington’s disease brain that are demonstrable immunocytochemically with antibodies to N-terminal huntingtin and to ubiquitin. Their distribution by region and by neuron type matches the known vulnerability pattern in Huntington’s disease, and it is thought that the presence of inclusions is a marker for future cell degeneration. We recently described a preferential loss of medium spiny neurons in neostriatal striosomes relative to the matrix, as defined by calbindin immunostaining, in early to middle stages of Huntington’s disease. We now show that ubiquitinated neuronal intranuclear inclusions are present in a greater proportion of the medium spiny neurons of striosomes than in those of the matrix in Huntington’s disease brains (Vonsattel grade 0–3). The proportion in striosomes correlates strongly with age at death, probably a reflection of CAG repeat length, whereas in the matrix the proportion with inclusions correlates with Vonsattel grade. The fmding of a preferential involvement of striosomal medium spiny neurons early in the course of disease is consistent both with the hypothesis of greater vulnerability of striosomal neurons to the pathogenic process in Huntington’s disease, and with the idea that the inclusions are harbingers of cell death.
KeywordsRepeat Length Middle Stage Medium Spiny Neuron Neuronal Intranuclear Inclusion Vulnerability Pattern
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