Neurofilament light chain as a potential biomarker for monitoring neurodegeneration in X-linked adrenoleukodystrophy.
Neurofilament light chain as a potential biomarker for monitoring neurodegeneration in X-linked adrenoleukodystrophy.
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DOI：
10.1038/s41467-021-22114-2
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发表时间：
2021-03-22
影响因子：
16.6
通讯作者：
Berger J
中科院分区：
文献类型：
--
作者：
Weinhofer I;Rommer P;Zierfuss B;Altmann P;Foiani M;Heslegrave A;Zetterberg H;Gleiss A;Musolino PL;Gong Y;Forss-Petter S;Berger T;Eichler F;Aubourg P;Köhler W;Berger J
X-连锁肾上腺脑白质营养不良（X-ALD）是最常见的脑白色物质单基因遗传性疾病，具有高度可变性，从缓慢进行性肾上腺脊髓神经病（AMN）到危及生命的炎性脑脱髓鞘（CALD）。在这项涉及94名X-ALD患者和55名对照的研究中，我们测试了血浆/血清神经丝轻链蛋白（NfL）是否构成早期区分生物标志物。在AMN中，我们发现NfL中度升高，其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与后来发展为CALD的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，神经性低NfL揭示了以前未被认识到的慢性CALD病程，伴有缓慢进行性髓鞘破坏。在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，因此构成了一个潜在的替代生物标志物，可能有助于临床决策和治疗开发。X-连锁肾上腺脑白质营养不良（X-ALD）是一种高度可变的进行性神经退行性疾病。在这项研究中，神经丝轻链蛋白（NfL）被确定为一个潜在的早期区分生物标志物。
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-linked adrenoleukodystophy (X-ALD) is a highly variable, progressive neurodegenerative disorder. In this study, neurofilament light chain protein (NfL) was identified as a potential early distinguishing biomarker.
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DOI：
10.1056/nejmoa1700554
发表时间：
2017-10-26
期刊：
The New England journal of medicine
影响因子：
--
作者：
Eichler F;Duncan C;Musolino PL;Orchard PJ;De Oliveira S;Thrasher AJ;Armant M;Dansereau C;Lund TC;Miller WP;Raymond GV;Sankar R;Shah AJ;Sevin C;Gaspar HB;Gissen P;Amartino H;Bratkovic D;Smith NJC;Paker AM;Shamir E;O'Meara T;Davidson D;Aubourg P;Williams DA
通讯作者：
Williams DA
影响因子：
29
作者：
Absinta, Martina;Sati, Pascal;Reich, Daniel S.
通讯作者：
Reich, Daniel S.
DOI：
10.1097/00005072-199211000-00007
发表时间：
1992-11-01
影响因子：
3.2
作者：
POWERS, JM;LIU, Y;MOSER, HW
通讯作者：
MOSER, HW
影响因子：
3.5
作者：
Moser, Ann B.;Jones, Richard O.;Raymond, Gerald V.
通讯作者：
Raymond, Gerald V.
影响因子：
2.6
作者：
Meyer-Moock S;Feng YS;Maeurer M;Dippel FW;Kohlmann T
通讯作者：
Kohlmann T