Linking white matter and deep gray matter alterations in premanifest Huntington disease.
Linking white matter and deep gray matter alterations in premanifest Huntington disease.
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DOI：
10.1016/j.nicl.2016.02.014
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
PREDICT-HD Investigators and Coordinators of the Huntington Study Group
中科院分区：
文献类型：
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作者：
Faria AV;Ratnanather JT;Tward DJ;Lee DS;van den Noort F;Wu D;Brown T;Johnson H;Paulsen JS;Ross CA;Younes L;Miller MI;PREDICT-HD Investigators and Coordinators of the Huntington Study Group
亨廷顿病（HD）是一种致死性进行性神经退行性疾病，其仅可进行对症治疗。更好地了解病理学和生物标志物的鉴定将促进疾病修饰治疗的发展。HD可能是开发生物标志物的神经退行性疾病的良好模型，因为它是一种由单基因突变引起的具有完全突变的常染色体显性疾病，其中神经退行性过程可以在明显疾病的体征和症状发作前多年进行评估。先前的MRI研究已经发现了在表现前阶段开始的灰色和白色物质的异常。然而，对这些异常在时间和空间上如何相关的理解仍然不完整。在这项研究中，我们结合了深部灰质形态学和白色物质的DTI分析，以提供一个更好的映射的病理在深部灰质和皮质下白色物质在前驱HD。我们使用了来自PREDICT-HD数据库的296次MRI扫描。通过基于表面的形态测定法分析深部灰质、丘脑、海马和丘脑核中的萎缩，同时使用（ii）基于纤维束成像的分析和（iii）基于全脑图谱的分析在（i）这些结构周围的感兴趣区域中分析白色物质异常。我们检测到萎缩的深层灰质，特别是在壳核，从早期premanifest阶段。萎缩的程度和效应量在接触CAG扩增突变效应时间较长的病例中更大（通过更大的CAP评分评估），并且先于白色物质的可检测异常。在预测的显性HD发作附近，MD增加是广泛的，在深部和后部白色物质中指数最高。HD脑异常的这种类型的体内宏观映射可以潜在地指示何时和何处可以靶向治疗以延迟发作或减缓疾病进展。追踪HD的时间和空间进展对于设计治疗方案至关重要。我们分析皮质下灰质的形状和DTI在296先觉HD个人。深层灰质的形状变化发生在非常早期的预显阶段。大脑差异的体内映射可能表明何时何地可以靶向治疗。
Huntington disease (HD) is a fatal progressive neurodegenerative disorder for which only symptomatic treatment is available. A better understanding of the pathology, and identification of biomarkers will facilitate the development of disease-modifying treatments. HD is potentially a good model of a neurodegenerative disease for development of biomarkers because it is an autosomal-dominant disease with complete penetrance, caused by a single gene mutation, in which the neurodegenerative process can be assessed many years before onset of signs and symptoms of manifest disease. Previous MRI studies have detected abnormalities in gray and white matter starting in premanifest stages. However, the understanding of how these abnormalities are related, both in time and space, is still incomplete. In this study, we combined deep gray matter shape diffeomorphometry and white matter DTI analysis in order to provide a better mapping of pathology in the deep gray matter and subcortical white matter in premanifest HD. We used 296 MRI scans from the PREDICT-HD database. Atrophy in the deep gray matter, thalamus, hippocampus, and nucleus accumbens was analyzed by surface based morphometry, and while white matter abnormalities were analyzed in (i) regions of interest surrounding these structures, using (ii) tractography-based analysis, and using (iii) whole brain atlas-based analysis. We detected atrophy in the deep gray matter, particularly in putamen, from early premanifest stages. The atrophy was greater both in extent and effect size in cases with longer exposure to the effects of the CAG expansion mutation (as assessed by greater CAP-scores), and preceded detectible abnormalities in the white matter. Near the predicted onset of manifest HD, the MD increase was widespread, with highest indices in the deep and posterior white matter. This type of in-vivo macroscopic mapping of HD brain abnormalities can potentially indicate when and where therapeutics could be targeted to delay the onset or slow the disease progression. Tracing temporal and spatial progression of HD is essential to design therapeutics. We analyze subcortical gray matter shape and DTI in 296 premanifest HD individuals. Changes in the shape of deep gray matter occur since the very early premanifest stages. The in-vivo mapping of brain differences potentially indicate when and where therapeutics could be targeted.