HEREDITARY DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY - DETECTION OF WIDESPREAD UBIQUITINATED NEURONAL AND GLIAL INTRANUCLEAR INCLUSIONS IN THE BRAIN

`We examined the brains and spinal cords of seven patients with clinic opathologically and genetically confirmed hereditary dentatorubral-pal lidoluysian atrophy (DRPLA) using an antibody against ubiquitin, and f ound small, round immunoreactive intranuclear inclusions in both neuro ns and glial cells in various brain regions. Ubiquitinated neuronal in tranuclear inclusions (uNIIs) were consistently found in the striatum, the pontine nuclei, the inferior olivary complex, the cerebellar cort ex and the dentate nucleus. Ubiquitinated glial intranuclear inclusion s (uGIIs) were found less frequently than uNIIs. Most of the inclusion -bearing nuclei were of an astrocytic nature. Immunostaining with an a ntibody against DRPLA protein revealed similar immunoreactive neuronal and glial intranuclear inclusions, but in much smaller in numbers com pared with uNIIs and uGIIs. Electron microscopy showed that such inclu sions were composed of granular and filamentous structures. These find ings strongly suggest that, in DRPLA, the occurrence of uNIIs and uGII s is directly related to the causative gene abnormality (an expanded C AG repeat encoding polyglutamine), that neurons are affected much more widely than previously recognized and that glial cells are also invol ved in the disease process.