2023,
Movement Disorders.
DOI:
10.1002/mds.29430
Application Value of Serum Neurofilament Light Protein for Disease Staging in Huntington's Disease
Xiao‐Yan Li, Yu‐Feng Bao, Juan‐Juan Xie, Bin Gao, Shu‐Xia Qian, Yi Dong, Zhi‐Ying Wu
Abstract:
Abstract Background Neurofilament light protein (NfL) has been proven to be a sensitive biomarker for Huntington's disease (HD). However, these studies did not include HD patients at advanced stages or with larger CAG repeats (>50), leading to a knowledge gap of the characteristics of NfL. Methods Serum NfL (sNfL) levels were quantified using an ultrasensitive immunoassay. Participants were assessed by clinical scales and 7.0 T magnetic resonance imaging. Longitudinal samples and clinical data were obtained. Results Baseline samples were available from 110 controls, 90 premanifest HD (pre‐HD) and 137 HD individuals. We found levels of sNfL significantly increased in HD compared to pre‐HD and controls (both P < 0.0001). The increase rates of sNfL were differed by CAG repeat lengths. However, there was no difference in sNfL levels in manifest HD from early to late stages. In addition, sNfL levels were associated with cognitive measures in pre‐HD and manifest HD group, respectively. The increased levels of sNfL were also closely related to microstructural changes in white matter. In the longitudinal analysis, baseline sNfL did not correlate with subsequent clinical function decline. Random forest analysis revealed that sNfL had good power for predicting disease onset. Conclusions Although sNfL levels are independent of disease stages in manifest HD, it is still an optimal indicator for predicting disease onset and has potential use as a surrogate biomarker of treatment effect in clinical trials. © 2023 International Parkinson and Movement Disorder Society.
2024-01-31 18:29:00
盼盼:
https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29430本文应用浙江大学第二附属医院神经内科随访的亨廷顿病人信息，构建模型，经过分析发现患者血液中神经丝轻蛋白（Neurofilament light protein）可以预测Huntington's disease亨廷顿病人的发病年龄。这个蛋白主要跟发病年龄，发病前脑白质病变程度有关，但是跟发病之后的严重程度没有统计学关联。亨廷顿基因的串联重复序列数目越多，发病年龄也越早，而发病前重复序列数目多的患者，其NFL水平也比较高。总之，NFL可以作为预测亨廷顿病发病年龄的生物学marker，是本文解决的一个重要临床问题。