Department of Anatomy with Radiology, University of Auckland, and Department of Forensic Pathology, Auckland City Hospital, Private Bag 92019, Auckland, New Zealand.
Brain. 2010 Apr;133(Pt 4):1094-110. doi: 10.1093/brain/awq047.
Huntington's disease is an autosomal dominant inherited neurodegenerative disease with motor symptoms that are variably co-expressed with mood and cognitive symptoms, and in which variable neuronal degeneration is also observed in the basal ganglia and the cerebral cortex. We have recently shown that the variable symptomatology in Huntington's disease correlates with the variable compartmental pattern of GABAA receptor and cell loss in the striatum. To determine whether the phenotypic variability in Huntington's disease is also related to variable neuronal degeneration in the cerebral cortex, we undertook a double-blind study using unbiased stereological cell counting methods to determine the pattern of cell loss in the primary motor and anterior cingulate cortices in the brains of 12 cases of Huntington's disease and 15 controls, and collected detailed data on the clinical symptomatology of the patients with Huntington's disease from family members and clinical records. The results showed a significant association between: (i) pronounced motor dysfunction and cell loss in the primary motor cortex; and (ii) major mood symptomatology and cell loss in the anterior cingulate cortex. This association held for both total neuronal loss (neuronal N staining) and pyramidal cell loss (SMI32 staining), and also correlated with marked dystrophic changes in the remaining cortical neurons. There was also an association between cortical cell loss and striatal neuropathological grade, but no significant association with CAG repeat length in the Huntington's disease gene. These findings suggest that the heterogeneity in clinical symptomatology that characterizes Huntington's disease is associated with variation in the extent of cell loss in the corresponding functional regions of the cerebral cortex whereby motor dysfunction correlates with primary motor cortex cell loss and mood symptomatology is associated with cell loss in the cingulate cortex.
亨廷顿病是一种常染色体显性遗传的神经退行性疾病，具有运动症状，这些症状与情绪和认知症状不同时出现，并且在基底神经节和大脑皮层中也观察到可变的神经元变性。我们最近表明，亨廷顿病的可变症状与纹状体中 GABA A 受体和细胞丢失的可变隔室模式相关。为了确定亨廷顿病的表型变异性是否也与大脑皮层中的可变神经元变性有关，我们进行了一项双盲研究，使用无偏立体学细胞计数方法来确定 12 例亨廷顿病和 15 例对照者大脑初级运动和前扣带回皮层的细胞丢失模式，并从家庭成员和临床记录中收集了亨廷顿病患者的详细临床症状数据。结果表明，（i）明显的运动功能障碍与初级运动皮层的细胞丢失之间存在显著相关性；（ii）主要的情绪症状与前扣带皮层的细胞丢失之间存在显著相关性。这种关联既适用于总神经元丢失（神经元 N 染色），也适用于锥体神经元丢失（SMI32 染色），并且与剩余皮质神经元中的明显退行性变化相关。皮质神经元丢失与纹状体神经病理学分级之间也存在关联，但与亨廷顿病基因中的 CAG 重复长度无显著关联。这些发现表明，亨廷顿病特征性的临床症状异质性与大脑皮层相应功能区域细胞丢失的程度有关，其中运动功能障碍与初级运动皮层细胞丢失相关，而情绪症状与扣带皮层细胞丢失相关。
