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）的晚期，但这种症状的病理基础尚不清楚。为了阐明阿尔茨海默病中肌阵挛的神经病理底物，我们定量评估了8例患有肌阵挛的阿尔茨海默病患者、10例无肌阵挛的阿尔茨海默病患者和9例对照者小脑齿状核吻侧和尾侧神经元的密度和体积，并区分了大小神经元。肌阵挛性AD组吻侧大神经元数量密度和总神经元数量（吻侧和尾侧）显著大于非肌阵挛性AD组。两组间小神经元密度无显著差异。伴有肌阵挛的AD小神经元与大神经元总数之比明显低于无肌阵挛的AD。肌阵挛性阿尔茨海默病鼻侧大神经元的平均神经元体积明显大于非肌阵挛性阿尔茨海默病。相反，肌阵挛性AD的吻侧小神经元体积明显低于非肌阵挛性AD。本研究首次发现AD伴肌阵挛患者齿状核中大神经元平均体积增大，小神经元平均体积减小，小神经元与大神经元之比发生变化。小神经元与大神经元比例的不平衡以及齿状核中这些神经元的形态改变可能是AD中肌缩的病理底物。

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.