Cerebellar dentate nucleus in Alzheimer's disease with myoclonus.

Although myoclonus commonly occurs in a later stage of Alzheimer's disease (AD), the pathological basis of this symptom is still unclear. In order to elucidate the neuropathological substrate of myoclonus in AD, we quantitatively assessed neuronal density and volume, with a discrimination between small and large neurons, at the rostral and caudal parts in the cerebellar dentate nucleus of 8 AD patients with myoclonus, 10 AD patients without myoclonus and 9 controls, using stereological probes. The neuronal numerical density of the large neurons at the rostral part and of total counts (rostral and caudal parts) in the myoclonic AD group were significantly greater than in the nonmyoclonic AD group. There were no significant differences in the density of small neurons between the two AD groups. The ratio of small neurons to large neurons (S/L ratio) of total counts was significantly lower in AD with myoclonus than in AD without myoclonus. The mean neuronal volume of the large neurons at the rostral part was significantly greater in myoclonic AD than in nonmyoclonic AD. Conversely, the volume of the small neurons at the rostral part was significantly lower in myoclonic AD than in nonmyoclonic AD. This study, for the first time, shows an increase in mean volume of large neurons and a decrease in mean volume of small neurons as well as a change in the S/L ratio in the dentate nucleus in AD with myoclonus. An imbalance in the S/L ratio as well as morphological changes of these neurons in the dentate nucleus may contribute to the pathological substrate of myoclonus in AD.