Department of Electrical and Electronic Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, China.
Division of Neurobiology, Departments of Psychiatry, Neurology, Neuroscience and Pharmacology, and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Hum Brain Mapp. 2019 Apr 1;40(5):1419-1433. doi: 10.1002/hbm.24456. Epub 2018 Oct 30.
Huntington's disease (HD) involves preferential and progressive degeneration of striatum and other subcortical regions as well as regional cortical atrophy. It is caused by a CAG repeat expansion in the Huntingtin gene, and the longer the expansion the earlier the age of onset. Atrophy begins prior to manifest clinical signs and symptoms, and brain atrophy in premanifest expansion carriers can be studied. We employed a diffeomorphometric pipeline to contrast subcortical structures' morphological properties in a control group with three disease groups representing different phases of premanifest HD (far, intermediate, and near to onset) as defined by the length of the CAG expansion and the participant's age (CAG-Age-Product). A total of 1,428 magnetic resonance image scans from 694 participants from the PREDICT-HD cohort were used. We found significant region-specific atrophies in all subcortical structures studied, with the estimated abnormality onset time varying from structure to structure. Heterogeneous shape abnormalities of caudate nuclei were present in premanifest HD participants estimated furthest from onset and putaminal shape abnormalities were present in participants intermediate to onset. Thalamic, hippocampal, and amygdalar shape abnormalities were present in participants nearest to onset. We assessed whether the estimated progression of subcortical pathology in premanifest HD tracked specific pathways. This is plausible for changes in basal ganglia circuits but probably not for changes in hippocampus and amygdala. The regional shape analyses conducted in this study provide useful insights into the effects of HD pathology in subcortical structures.
亨廷顿病（HD）涉及纹状体和其他皮质下区域的优先和进行性退化以及区域性皮质萎缩。它是由亨廷顿基因中的 CAG 重复扩展引起的，扩展越长，发病年龄越早。萎缩发生在明显的临床体征和症状之前，并且可以研究前显型扩展携带者的脑萎缩。我们采用了一种差分形态测量学管道，以对比对照组和三个疾病组（根据 CAG 扩展的长度和参与者的年龄定义的前显型 HD 的不同阶段（远、中、接近发病））的皮质下结构的形态特征。总共使用了来自 PREDICT-HD 队列的 694 名参与者的 1428 个磁共振成像扫描。我们发现所有研究的皮质下结构都存在明显的区域特异性萎缩，估计异常起始时间因结构而异。前显型 HD 参与者的尾状核存在不均匀的形状异常，且发病时间最近的参与者的壳核形状异常。我们评估了前显型 HD 中的皮质下病理学的估计进展是否与特定途径相关。这对于基底节回路的变化是合理的，但对于海马体和杏仁核的变化可能不合理。本研究中的区域形状分析为皮质下结构中 HD 病理学的影响提供了有用的见解。
