CLINCOPATHOLOY OF MYOCLONUS IN ALZHEIMER'S DISEASE : A NEUROPATHOLOGICAL STUDY IN THE CEREBELLAR DENTATE NUCLEUS USING STEREOLOGCAL PROBES

虽然肌阵挛通常发生在阿尔茨海默病（AD）的后期，但这种症状的病理基础仍然不清楚。为了阐明AD肌阵挛的神经病理学底物，我们定量评估神经元的密度和体积，与小和大的神经元之间的歧视，在头侧和尾侧部分在小脑齿状核的8例AD患者肌阵挛，10例AD患者没有肌阵挛和9个对照，使用体视学探针。肌阵挛性AD组头端大神经元数密度和头端和尾端总神经元数密度均显著高于非肌阵挛性AD组。两组间小神经元密度差异无统计学意义。AD伴肌阵挛组小神经元与大神经元总数之比显著低于AD不伴肌阵挛组。肌阵挛性AD的嘴部大神经元的平均神经元体积显著大于非肌阵挛性AD。相反，肌阵挛性AD的嘴部小神经元的体积显著低于非肌阵挛性AD。这项研究首次，显示了大神经元平均体积的增加和小神经元平均体积的减少，以及齿状核中小神经元与大神经元比例的变化，AD伴肌阵挛。齿状核内神经元的大小比例失衡以及这些神经元的形态学改变可能是AD肌阵挛的病理基础。

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 eight AD patients with myoclonus, ten AD patients without myoclonus and nine 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 myoclonic AD group were significantly greater than in non-myoclonic 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 of total counts in AD with myoclonus significantly was lower than in AD without myoclonus. The mean neuronal volume of the large neurons at the rostral part in myoclonic AD was significantly greater than in non-myoclonic AD.Conversely, the volume of the small neurons at the rostral part in myoclonic AD was significantly lower than in non-myoclonic 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 ratio of small to large neurons in the dentate nucleus in AD with myoclonus. An imbalance in the proportion of small to large neurons as well as morphological changes of these neurons in the dentate nucleus may contribute to the pathological substrate of myoclonus in AD.