Department of Medical Genetics and Center for Rare Diseases, and Department of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China.
MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, China.
Mov Disord. 2023 Jul;38(7):1307-1315. doi: 10.1002/mds.29430. Epub 2023 May 6.
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.
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.
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.
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.
神经丝轻链蛋白（NfL）已被证明是亨廷顿病（HD）的一种敏感生物标志物。然而，这些研究并未纳入处于晚期或具有更大 CAG 重复（>50）的 HD 患者，因此存在 NfL 特征的知识空白。
使用超敏免疫测定法定量测定血清 NfL（sNfL）水平。通过临床量表和 7.0T 磁共振成像对参与者进行评估。获得纵向样本和临床数据。
基线样本来自 110 名对照、90 名前亨廷顿病（pre-HD）和 137 名 HD 个体。我们发现 HD 患者的 sNfL 水平明显高于 pre-HD 和对照组（均 P<0.0001）。sNfL 的增加率因 CAG 重复长度而异。然而，在从早期到晚期的显性 HD 中，sNfL 水平没有差异。此外，sNfL 水平与 pre-HD 和显性 HD 组的认知测量分别相关。sNfL 水平的升高也与白质的微观结构变化密切相关。在纵向分析中，基线 sNfL 与随后的临床功能下降无关。随机森林分析显示，sNfL 具有良好的预测疾病发作的能力。
尽管 sNfL 水平与显性 HD 中的疾病阶段无关，但它仍然是预测疾病发作的最佳指标，并且有潜力作为临床试验中治疗效果的替代生物标志物。©2023 国际帕金森病和运动障碍学会。
