HEREDITARY DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY - UBIQUITINATED FILAMENTOUS INCLUSIONS IN THE CEREBELLAR DENTATE NUCLEUS NEURONS

We examined the cerebellar dentate nucleus (CDN) in 16 patients with h ereditary dentatorubral-pallidoluysian atrophy (DRPLA), one of the neu rodegenerative diseases caused by expansion of a CAG repeat encoding a polyglutamine tract in the disease protein. In all patients, some CDN neurons were found to contain ubiquitinated filamentous inclusions in their cytoplasm. On hematoxylin and eosin preparations, these filamen tous inclusions were eosinophilic, basophilic or amphophilic, and were often found in areas of pale cytoplasm. Electron microscopy revealed that they consisted of bundles of filaments that were somewhat thicker than neurofilaments. These features of the present inclusions were in distinguishable from those of skein-like inclusions (SLI) previously d escribed in the lower motor neurons in sporadic amyotrophic lateral sc lerosis. We conclude that SLI can also occur in the CDN in DRPLA and b elieve that they reflect a characteristic pathological process in this disease.