血液中的神经丝轻蛋白可预测亨廷顿病的区域性萎缩。
Neurofilament light protein in blood predicts regional atrophy in Huntington disease.
机构信息
From the Huntington's Disease Research Centre (E.B.J., L.M.B., S.G., F.B.R., S.J.T., R.I.S., E.J.W.), UCL Institute of Neurology, London, UK; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Institut du Cerveau et de la Moelle épinière (A.D.), Sorbonne Universités, UPMC University Paris 06, UMRS 1127, INSERM, U 1127, CNRS, UMR 7225; APHP (A.D.), Genetics Department, Pitié-Salpêtrière University Hospital, Paris, France; Centre for Molecular Medicine and Therapeutics (B.R.L.), University of British Columbia, Vancouver, BC, Canada; Department of Neurology (R.A.R.), Leiden University, the Netherlands; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; and UK Dementia Research Institute (H.Z.), London, UK.
出版信息
Neurology. 2018 Feb 20;90(8):e717-e723. doi: 10.1212/WNL.0000000000005005. Epub 2018 Jan 24.
OBJECTIVE
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
目的
血浆中的神经丝轻链（NfL）蛋白已被提议作为包括亨廷顿病（HD）在内的多种疾病中神经退行性变的预后生物标志物。本研究调查了 HD 基因扩展携带者中与 NfL 相关的神经病理学的区域分布。
方法
我们在来自国际多中心 TRACK-HD 研究的 HD 基因扩展携带者的横断面（n = 198）和纵向（n = 177）数据中，检查了血浆中测量的 NfL 与区域特异性萎缩之间的关联。使用基于体素的形态计量学，我们测量了基线 NfL 水平与基线灰质和白质体积之间的关联；以及在接下来的 3 年内 HD 基因扩展携带者的灰质和白质的纵向变化。
结果
在控制了人口统计学因素后，我们发现 NfL 水平升高与皮质和皮质下灰质以及白质内的脑容量减少之间存在关联。在还控制了疾病进展的已知预测因素（年龄和 CAG 重复长度）后，关联仅限于尾状核和壳核。纵向来看，NfL 预测了随后的枕叶灰质萎缩和广泛的白质减少，这在纠正了其他疾病进展预测因素之前和之后都是如此。
结论
这些发现强调了 NfL 作为脑萎缩的动态标志物的价值，更广泛地提供了证据表明血浆 NfL 水平（候选血液生物标志物）与病理神经元变化之间存在强烈关联。
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