Department of Neurology, Jeonbuk National University Medical School and Hospital & Research Institute of Clinical Medicine of Jeonbuk National University - Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea.
Department of Neurology, Chungnam National University College of Medicine and Hospital, Daejeon, Republic of Korea.
J Neurol Sci. 2023 Sep 15;452:120744. doi: 10.1016/j.jns.2023.120744. Epub 2023 Jul 28.
To investigate neurofilament light chain (NfL), phosphorylated tau (p-Tau) and total tau (t-Tau) as plasma markers for clinical severity in Korean Huntington's disease (HD) cohort.
Genetically-confirmed 67 HD patients participated from 13 referral hospitals in South Korea. The subjects were evaluated with the Unified Huntington's Disease Rating Scale (UHDRS), total motor score (TMS) and total functional capacity (TFC), Mini-Mental Status Examination (K-MMSE), Montreal Cognitive Assessment (MoCA-K), and Beck's depression inventory (K-BDI). We measured plasma NfL, p-Tau and t-Tau concentrations using single-molecule array (SIMOA) assays. Stages of HD were classified based on UHDRS-TFC score and plasma markers were analyzed for correlation with clinical severity scales.
Plasma NfL was elevated in both 6 premanifest and 61 full manifest HD patients compared to the reference value, which increased further from premanifest to manifest HD groups. The NfL level was not significantly correlated with UHDRS TMS or TFC scores in manifest HD patients. Plasma p-Tau was also elevated in HD patients (p = 0.038). The level was the highest in stage III-V HD (n = 30) group (post-hoc p < 0.05). The p-Tau was correlated with UHDRS TFC scores (adjusted p = 0.002). Plasma t-Tau neither differed among the groups nor associated with any clinical variables.
This study supports plasma NfL being a biomarker for initial HD manifestation in Korean cohort, and a novel suggestion of plasma p-Tau as a potential biomarker reflecting the clinical severity in full-manifest HD.
探讨神经丝轻链（NfL）、磷酸化tau（p-Tau）和总 tau（t-Tau）作为韩国亨廷顿病（HD）队列临床严重程度的血浆标志物。
从韩国 13 家转诊医院招募了 67 名经基因确诊的 HD 患者。使用统一亨廷顿病评定量表（UHDRS）、总运动评分（TMS）和总功能能力（TFC）、简易精神状态检查（K-MMSE）、蒙特利尔认知评估（MoCA-K）和贝克抑郁量表（K-BDI）对受试者进行评估。我们使用单分子阵列（SIMOA）检测试剂盒测量血浆 NfL、p-Tau 和 t-Tau 浓度。根据 UHDRS-TFC 评分对 HD 分期，并分析血浆标志物与临床严重程度量表的相关性。
与参考值相比，6 例前显型和 61 例完全显型 HD 患者的血浆 NfL 升高，且从前显型到显型 HD 组进一步升高。在显型 HD 患者中，NfL 水平与 UHDRS TMS 或 TFC 评分无显著相关性。HD 患者的血浆 p-Tau 也升高（p=0.038）。在 III-V 期 HD（n=30）组中水平最高（事后检验 p<0.05）。p-Tau 与 UHDRS TFC 评分相关（调整后 p=0.002）。血浆 t-Tau 在各组之间无差异，也与任何临床变量无关。
本研究支持血浆 NfL 作为韩国队列中 HD 初始表现的生物标志物，以及血浆 p-Tau 作为反映全显型 HD 临床严重程度的潜在生物标志物的新提示。
