Centre for Brain Research, University of Auckland, Auckland, New Zealand.
Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New Zealand.
Ann Neurol. 2019 Mar;85(3):396-405. doi: 10.1002/ana.25413. Epub 2019 Feb 4.
Huntington disease (HD) is an autosomal dominant neurodegenerative disorder characterized by variable motor and behavioral symptoms attributed to major neuropathology of mainly the basal ganglia and cerebral cortex. The role of the cerebellum, a brain region involved in the coordination of movements, in HD neuropathology has been controversial. This study utilizes postmortem human brain tissue to investigate whether Purkinje cell degeneration in the neocerebellum is present in HD, and how this relates to disease symptom profiles.
Unbiased stereological counting methods were used to quantify the total number of Purkinje cells in 15 HD cases and 8 neurologically normal control cases. Based on their predominant symptoms, the HD cases were categorized into 2 groups: "motor" or "mood."
The results demonstrated a significant 43% loss of Purkinje cells in HD cases with predominantly motor symptoms, and no cell loss in cases showing a major mood phenotype. There was no significant correlation between Purkinje cell loss and striatal neuropathological grade, postmortem delay, CAG repeat in the IT15 gene, or age at death.
This study shows a compelling relationship between Purkinje cell loss in the HD neocerebellum and the HD motor symptom phenotype, which, together with our previous human brain studies on the same HD cases, provides novel perspectives interrelating and correlating the variable cerebellar, basal ganglia, and neocortical neuropathology with the variability of motor/mood symptom profiles in the human HD brain. ANN NEUROL 2019;85:396-405.
亨廷顿病（HD）是一种常染色体显性神经退行性疾病，其特征为运动和行为症状多变，主要归因于基底节和大脑皮层的主要神经病理学变化。小脑作为参与运动协调的脑区，在 HD 神经病理学中的作用一直存在争议。本研究利用人脑尸检组织来探究新小脑浦肯野细胞退化是否存在于 HD 中，以及其与疾病症状谱的关系。
采用无偏立体学计数方法，对 15 例 HD 病例和 8 例神经正常对照病例的浦肯野细胞总数进行了定量。根据其主要症状，将 HD 病例分为“运动”或“情绪”两组。
结果表明，主要表现为运动症状的 HD 病例中，浦肯野细胞显著丧失 43%，而主要表现为情绪表型的病例中则没有细胞丢失。浦肯野细胞丢失与纹状体神经病理学分级、尸检延迟、IT15 基因中的 CAG 重复、死亡年龄之间无显著相关性。
本研究显示 HD 新小脑浦肯野细胞丢失与 HD 运动症状表型之间存在强烈的关联，这与我们之前对同一批 HD 病例进行的人脑研究一起，为相关研究提供了新的视角，即变异性小脑、基底节和大脑皮层神经病理学与人类 HD 大脑中运动/情绪症状谱的变异性之间相互关联和相互关联。
