Neurofilament light protein in blood predicts regional atrophy in Huntington disease.
Neurofilament light protein in blood predicts regional atrophy in Huntington disease.
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DOI：
10.1212/wnl.0000000000005005
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发表时间：
2018-02-20
期刊：
影响因子：
9.9
通讯作者：
TRACK-HD Study Group
中科院分区：
文献类型：
--
作者：
Johnson EB;Byrne LM;Gregory S;Rodrigues FB;Blennow K;Durr A;Leavitt BR;Roos RA;Zetterberg H;Tabrizi SJ;Scahill RI;Wild EJ;TRACK-HD Study Group
血浆中的神经丝轻（NfL）蛋白已被提出作为许多病症（包括亨廷顿病（HD））中神经变性的预后生物标志物。本研究调查了HD基因扩增携带者中NfL相关神经病理学的区域分布。我们研究了国际多位点TRACK-HD研究中HD基因扩增携带者的横截面（n = 198）和纵向（n = 177）数据中血浆中测量的NfL与区域特异性萎缩之间的相关性。使用基于体素的形态测量法，我们测量了基线NfL水平与基线灰质和白色物质体积之间的关联;以及HD基因扩增携带者在随后3年中灰质和白色物质的纵向变化。在控制人口统计学因素后，在皮质和皮质下灰质以及白色物质中观察到NfL水平升高与脑体积减小之间的关联。在控制了已知的疾病进展预测因子（年龄和CAG重复长度）后，相关性仅限于尾状核和壳核。纵向上，NfL预测随后的枕叶灰质萎缩和广泛的白色物质减少，在校正疾病进展的其他预测因子之前和之后。这些发现突出了NfL作为脑萎缩的动态标志物的价值，并且更一般地，提供了血浆NfL水平（候选血液生物标志物）与病理性神经元变化之间的强关联的进一步证据。
Neurofilament light (NfL) protein in blood plasma has been proposed as a prognostic biomarker of neurodegeneration in a number of conditions, including Huntington disease (HD). This study investigates the regional distribution of NfL-associated neural pathology in HD gene expansion carriers. We examined associations between NfL measured in plasma and regionally specific atrophy in cross-sectional (n = 198) and longitudinal (n = 177) data in HD gene expansion carriers from the international multisite TRACK-HD study. Using voxel-based morphometry, we measured associations between baseline NfL levels and both baseline gray matter and white matter volume; and longitudinal change in gray matter and white matter over the subsequent 3 years in HD gene expansion carriers. After controlling for demographics, associations between increased NfL levels and reduced brain volume were seen in cortical and subcortical gray matter and within the white matter. After also controlling for known predictors of disease progression (age and CAG repeat length), associations were limited to the caudate and putamen. Longitudinally, NfL predicted subsequent occipital gray matter atrophy and widespread white matter reduction, both before and after correction for other predictors of disease progression. These findings highlight the value of NfL as a dynamic marker of brain atrophy and, more generally, provide further evidence of the strong association between plasma NfL level, a candidate blood biomarker, and pathologic neuronal change.