Department of Neurology, Gunma University Graduate School of Medicine, Gunma, Japan.
Department of Neurology, Geriatrics Research Institute and Hospital, Gunma, Japan.
J Neurol Sci. 2024 Aug 15;463:123137. doi: 10.1016/j.jns.2024.123137. Epub 2024 Jul 15.
Blood neurofilament light chain (NfL) is a minimally invasive, but highly sensitive biomarker of neurological diseases. However, diseases and neurological damage associated with increased NfL remain unclear. Therefore, the present study investigated factors associated with increased plasma NfL levels in various neurological diseases, focal lesions and pathological processes.
This was a retrospective cohort study on 410 participants with various neurological diseases and 17 healthy and cognitively unimpaired controls (HCU). Plasma samples were analyzed to measure NfL using ECL immunoassay. The focal lesions were classified as the cerebrum, cerebellum, brainstem, meninges, spinal cord, peripheral nerves, neuromuscular junction, and muscles based on medical records. A multiple regression analysis and receiver operating characteristic curve (ROC) analysis were performed to investigate whether plasma NfL levels predict specific diseases and focal lesions.
Plasma NfL levels discriminated between the HCU and all disease groups (area under the curve (AUC), 0.97), with a cut-off value of 63.4 pg/mL. A multiple regression analysis of focal lesions adjusted by pathogenic processes showed that brainstem and peripheral nerve involvement was associated with higher plasma NfL levels. A cut-off value of 53.8 pg/mL of NfL discriminated between the HCU and neurological disease group except for brainstem or peripheral disorders (AUC 0.962), while a cut-off value of 208.0 pg/mL distinguished this group from brainstem or peripheral nervous system disorders (AUC 0.716).
These results demonstrate that plasma NfL has a potential to be a highly sensitive biomarker for neurological diseases and focal lesions.
血液神经丝轻链（NfL）是一种微创但高度敏感的神经疾病生物标志物。然而，与 NfL 升高相关的疾病和神经损伤仍不清楚。因此，本研究旨在探讨各种神经疾病、局灶性病变和病理过程中与血浆 NfL 水平升高相关的因素。
这是一项回顾性队列研究，纳入了 410 名患有各种神经疾病的患者和 17 名健康且认知功能正常的对照组（HCU）。通过 ECL 免疫测定法分析血浆样本以测量 NfL。根据病历将局灶性病变分为大脑、小脑、脑干、脑膜、脊髓、周围神经、神经肌肉接头和肌肉。采用多元回归分析和受试者工作特征曲线（ROC）分析，以探讨血浆 NfL 水平是否可以预测特定疾病和局灶性病变。
血浆 NfL 水平可区分 HCU 和所有疾病组（曲线下面积（AUC）为 0.97），截断值为 63.4 pg/mL。对经病理过程调整的局灶性病变进行多元回归分析显示，脑干和周围神经受累与血浆 NfL 水平升高相关。NfL 的截断值为 53.8 pg/mL 可区分 HCU 和除脑干或周围神经障碍以外的神经疾病组（AUC 为 0.962），而截断值为 208.0 pg/mL 可区分该组与脑干或周围神经系统障碍（AUC 为 0.716）。
这些结果表明，血浆 NfL 有可能成为神经疾病和局灶性病变的高度敏感生物标志物。
