Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Vienna, Austria.
Department of Neurology, Medical University of Vienna, Vienna, Austria.
Nat Commun. 2021 Mar 22;12(1):1816. doi: 10.1038/s41467-021-22114-2.
X-linked adrenoleukodystrophy (X-ALD), the most frequent monogenetic disorder of brain white matter, is highly variable, ranging from slowly progressive adrenomyeloneuropathy (AMN) to life-threatening inflammatory brain demyelination (CALD). In this study involving 94 X-ALD patients and 55 controls, we tested whether plasma/serum neurofilament light chain protein (NfL) constitutes an early distinguishing biomarker. In AMN, we found moderately elevated NfL with increased levels reflecting higher grading of myelopathy-related disability. Intriguingly, NfL was a significant predictor to discriminate non-converting AMN from cohorts later developing CALD. In CALD, markedly amplified NfL levels reflected brain lesion severity. In rare cases, atypically low NfL revealed a previously unrecognized smoldering CALD disease course with slowly progressive myelin destruction. Upon halt of brain demyelination by hematopoietic stem cell transplantation, NfL gradually normalized. Together, our study reveals that blood NfL reflects inflammatory activity and progression in CALD patients, thus constituting a potential surrogate biomarker that may facilitate clinical decisions and therapeutic development.
X 连锁肾上腺脑白质营养不良（X-ALD）是最常见的脑白质单基因疾病，具有高度变异性，从缓慢进展的肾上腺脑神经病（AMN）到危及生命的炎症性脑脱髓鞘（CALD）不等。在这项涉及 94 名 X-ALD 患者和 55 名对照者的研究中，我们测试了血浆/血清神经丝轻链蛋白（NfL）是否构成早期鉴别生物标志物。在 AMN 中，我们发现 NfL 中度升高，水平升高反映了脊髓病相关残疾的更高分级。有趣的是，NfL 是区分非转化 AMN 与后来发生 CALD 队列的重要预测因子。在 CALD 中，明显放大的 NfL 水平反映了脑损伤的严重程度。在极少数情况下，异常低的 NfL 揭示了以前未被认识的隐匿性 CALD 疾病过程，伴有缓慢进展的髓鞘破坏。通过造血干细胞移植停止脑脱髓鞘后，NfL 逐渐正常化。总之，我们的研究表明，血液 NfL 反映了 CALD 患者的炎症活动和进展，因此构成了一种潜在的替代生物标志物，可能有助于临床决策和治疗的发展。
