症状前肌萎缩侧索硬化症的神经丝及基因型的影响

IF 2.5 4区 医学 Q2 CLINICAL NEUROLOGY Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration Pub Date : 2019-08-21 DOI:10.1080/21678421.2019.1646769
M. Benatar, J. Wuu, V. Lombardi, A. Jeromin, R. Bowser, P. Andersen, A. Malaspina
{"title":"症状前肌萎缩侧索硬化症的神经丝及基因型的影响","authors":"M. Benatar, J. Wuu, V. Lombardi, A. Jeromin, R. Bowser, P. Andersen, A. Malaspina","doi":"10.1080/21678421.2019.1646769","DOIUrl":null,"url":null,"abstract":"Abstract Objective. To evaluate serum and cerebrospinal fluid (CSF) levels of phosphorylated neurofilament heavy (pNfH), and to compare these to levels of neurofilament light (NfL), as biomarkers of pre-symptomatic ALS. Design. The study population includes 34 controls, 79 individuals at-risk for ALS, 22 ALS patients, and 14 phenoconverters. At-risk individuals are enrolled through Pre-Symptomatic Familial ALS (Pre-fALS), a longitudinal natural history and biomarker study of individuals who are carriers of any ALS-associated gene mutation, but who demonstrate no clinical evidence of disease at the time of enrollment. pNfH and NfL in serum and CSF were quantified using established enzyme-linked immunosorbent assays. Results. There is a longitudinal increase in serum pNfH in advance of the emergence of clinically manifest ALS. A similar pattern is observed for NfL, but with the absolute levels also frequently exceeding a normative threshold. Although CSF data are more sparse, similar patterns are observed for both neurofilaments, with absolute levels exceeding a normative threshold prior to phenoconversion. In serum, these changes are observed in the 6–12 months prior to disease among SOD1 A4V mutation carriers, and as far back as 2 and 3.5 years, respectively, in individuals with a FUS c.521del6 mutation and a C9ORF72 hexanucleotide repeat expansion. Conclusions. Serum and CSF pNfH increase prior to phenoconversion. In CSF, the temporal course of these changes is similar to NfL. In serum, however, pNfH is less sensitive to pre-symptomatic disease than NfL. The duration of pre-symptomatic disease, as defined by changes in neurofilaments, may vary depending on underlying genotype.","PeriodicalId":7740,"journal":{"name":"Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2019-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678421.2019.1646769","citationCount":"66","resultStr":"{\"title\":\"Neurofilaments in pre-symptomatic ALS and the impact of genotype\",\"authors\":\"M. Benatar, J. Wuu, V. Lombardi, A. Jeromin, R. Bowser, P. Andersen, A. Malaspina\",\"doi\":\"10.1080/21678421.2019.1646769\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Abstract Objective. To evaluate serum and cerebrospinal fluid (CSF) levels of phosphorylated neurofilament heavy (pNfH), and to compare these to levels of neurofilament light (NfL), as biomarkers of pre-symptomatic ALS. Design. The study population includes 34 controls, 79 individuals at-risk for ALS, 22 ALS patients, and 14 phenoconverters. At-risk individuals are enrolled through Pre-Symptomatic Familial ALS (Pre-fALS), a longitudinal natural history and biomarker study of individuals who are carriers of any ALS-associated gene mutation, but who demonstrate no clinical evidence of disease at the time of enrollment. pNfH and NfL in serum and CSF were quantified using established enzyme-linked immunosorbent assays. Results. There is a longitudinal increase in serum pNfH in advance of the emergence of clinically manifest ALS. A similar pattern is observed for NfL, but with the absolute levels also frequently exceeding a normative threshold. Although CSF data are more sparse, similar patterns are observed for both neurofilaments, with absolute levels exceeding a normative threshold prior to phenoconversion. In serum, these changes are observed in the 6–12 months prior to disease among SOD1 A4V mutation carriers, and as far back as 2 and 3.5 years, respectively, in individuals with a FUS c.521del6 mutation and a C9ORF72 hexanucleotide repeat expansion. Conclusions. Serum and CSF pNfH increase prior to phenoconversion. In CSF, the temporal course of these changes is similar to NfL. In serum, however, pNfH is less sensitive to pre-symptomatic disease than NfL. The duration of pre-symptomatic disease, as defined by changes in neurofilaments, may vary depending on underlying genotype.\",\"PeriodicalId\":7740,\"journal\":{\"name\":\"Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2019-08-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1080/21678421.2019.1646769\",\"citationCount\":\"66\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/21678421.2019.1646769\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/21678421.2019.1646769","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 66

摘要

摘要目的。评估血清和脑脊液(CSF)磷酸化神经丝重(pNfH)水平,并将其与神经丝轻(NfL)水平进行比较,作为症状前ALS的生物标志物。设计。研究人群包括34名对照组、79名ALS高危个体、22名ALS患者和14名表型转化者。有风险的个体通过症状前家族性ALS (Pre-fALS)纳入研究,这是一项纵向自然病史和生物标志物研究,研究对象是任何ALS相关基因突变携带者,但在入组时没有临床疾病证据。采用已建立的酶联免疫吸附法定量血清和脑脊液中的pNfH和NfL。结果。在临床表现的ALS出现之前,血清pNfH呈纵向上升趋势。在NfL中也观察到类似的模式,但其绝对水平也经常超过规范阈值。虽然脑脊液数据比较稀疏,但在两种神经丝中观察到相似的模式,绝对水平超过表型转化前的标准阈值。在血清中,SOD1 A4V突变携带者在发病前6-12个月观察到这些变化,在FUS c.521del6突变和C9ORF72六核苷酸重复扩增的个体中分别可追溯到2年和3.5年。结论。血清和脑脊液pNfH在表型转化前升高。在脑脊液中,这些变化的时间过程与NfL相似。然而,在血清中,pNfH对症状前疾病的敏感性低于NfL。症状前疾病的持续时间,由神经纤维的变化所定义,可能因潜在的基因型而异。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Neurofilaments in pre-symptomatic ALS and the impact of genotype
Abstract Objective. To evaluate serum and cerebrospinal fluid (CSF) levels of phosphorylated neurofilament heavy (pNfH), and to compare these to levels of neurofilament light (NfL), as biomarkers of pre-symptomatic ALS. Design. The study population includes 34 controls, 79 individuals at-risk for ALS, 22 ALS patients, and 14 phenoconverters. At-risk individuals are enrolled through Pre-Symptomatic Familial ALS (Pre-fALS), a longitudinal natural history and biomarker study of individuals who are carriers of any ALS-associated gene mutation, but who demonstrate no clinical evidence of disease at the time of enrollment. pNfH and NfL in serum and CSF were quantified using established enzyme-linked immunosorbent assays. Results. There is a longitudinal increase in serum pNfH in advance of the emergence of clinically manifest ALS. A similar pattern is observed for NfL, but with the absolute levels also frequently exceeding a normative threshold. Although CSF data are more sparse, similar patterns are observed for both neurofilaments, with absolute levels exceeding a normative threshold prior to phenoconversion. In serum, these changes are observed in the 6–12 months prior to disease among SOD1 A4V mutation carriers, and as far back as 2 and 3.5 years, respectively, in individuals with a FUS c.521del6 mutation and a C9ORF72 hexanucleotide repeat expansion. Conclusions. Serum and CSF pNfH increase prior to phenoconversion. In CSF, the temporal course of these changes is similar to NfL. In serum, however, pNfH is less sensitive to pre-symptomatic disease than NfL. The duration of pre-symptomatic disease, as defined by changes in neurofilaments, may vary depending on underlying genotype.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
5.40
自引率
10.70%
发文量
64
期刊介绍: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration is an exciting new initiative. It represents a timely expansion of the journal Amyotrophic Lateral Sclerosis in response to the clinical, imaging pathological and genetic overlap between ALS and frontotemporal dementia. The expanded journal provides outstanding coverage of research in a wide range of issues related to motor neuron diseases, especially ALS (Lou Gehrig’s disease) and cognitive decline associated with frontotemporal degeneration. The journal also covers related disorders of the neuroaxis when relevant to these core conditions.
期刊最新文献
The correlation between social support, coping style, advance care planning readiness, and quality of life in patients with amyotrophic lateral sclerosis: a cross-sectional study. Effects of COVID-19 on motor neuron disease mortality in the United States: a population-based cross-sectional study SOD1 gene screening in ALS – frequency of mutations, patients’ attitudes to genetic information and transition to tofersen treatment in a multi-center program How to break the news in amyotrophic lateral sclerosis/motor neuron disease: practical guidelines from experts A nurse coaching intervention to improve support to individuals living with ALS.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1