Yin Jin-Hui, Cao Ling-Xiao, Liu Ya-Ou, Huang Yue
Human Brain and Tissue Bank, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Mov Disord. 2025 Jul;40(7):1409-1419. doi: 10.1002/mds.30194. Epub 2025 Apr 9.
The aim was to investigate if glymphatic function is impaired in patients with Huntington's disease (HD) and its clinical relevance.
Forty-nine subjects carrying mutant Huntingtin (mHTT), comprising 35 manifest (mHD) and 14 pre-manifest (PreHD), and 35 healthy controls (HC) were recruited in this study. The diffusion along perivascular spaces (ALPS) index and the percentage of perivascular space in the basal ganglia (pPVS_BG) were obtained in different groups. The discrimination effects of ALPS index were detected using receiver operating characteristic (ROC) analysis, and the correlations of ALPS index with clinical features of HD were further analyzed.
ALPS index was decreased in mHTT carriers compared to HCs, and it was lower in mHD compared to PreHD patients. ROC analysis showed that the ALPS index could discriminate mHTT from HC (AUC [area under the curve] = 0.903), mHD from PreHD (AUC = 0.886), and PreHD from controls (AUC = 0.755). Lower ALPS index correlated with greater disease burden, severity of the disease, lager pPVS_BG, and lower brain volume and thickness of cortices. Regression analysis showed that ALPS index could predict the performance of motor and cognitive functions. Mediation analysis revealed that ALPS partially mediated the effects of CAG repeat and age on the cognitive decline in HD.
This study demonstrated that the impairment of the glymphatic system, especially in the paraventricular white matter and BG, was correlated with the clinical manifestations, disease burden, and brain structural changes in mHTT carriers. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
目的是研究亨廷顿舞蹈病（HD）患者的类淋巴功能是否受损及其临床相关性。
本研究招募了49名携带突变型亨廷顿蛋白（mHTT）的受试者，其中包括35名显性患者（mHD）和14名症状前患者（PreHD），以及35名健康对照者（HC）。在不同组中获得沿血管周围间隙扩散（ALPS）指数和基底节区血管周围间隙百分比（pPVS_BG）。使用受试者工作特征（ROC）分析检测ALPS指数的鉴别效果，并进一步分析ALPS指数与HD临床特征的相关性。
与HC相比，mHTT携带者的ALPS指数降低，与PreHD患者相比，mHD患者的ALPS指数更低。ROC分析表明，ALPS指数可区分mHTT与HC（曲线下面积[AUC]=0.903）、mHD与PreHD（AUC=0.886）以及PreHD与对照者（AUC=0.755）。较低的ALPS指数与更大的疾病负担、疾病严重程度、更大的pPVS_BG以及更低的脑容量和皮质厚度相关。回归分析表明，ALPS指数可预测运动和认知功能表现。中介分析显示，ALPS部分介导了CAG重复序列和年龄对HD认知衰退的影响。
本研究表明，类淋巴系统的损伤，尤其是在脑室旁白质和基底节区，与mHTT携带者的临床表现、疾病负担和脑结构变化相关。©2025作者。《运动障碍》由Wiley Periodicals LLC代表国际帕金森和运动障碍协会出版。
