Molecular signatures of normal pressure hydrocephalus: a large-scale proteomic analysis of cerebrospinal fluid.

IF 5.9 1区 医学 Q1 NEUROSCIENCES Fluids and Barriers of the CNS Pub Date : 2024-08-08 DOI:10.1186/s12987-024-00561-5
Aida Kamalian, Siavash Shirzadeh Barough, Sara G Ho, Marilyn Albert, Mark G Luciano, Sevil Yasar, Abhay Moghekar
{"title":"Molecular signatures of normal pressure hydrocephalus: a large-scale proteomic analysis of cerebrospinal fluid.","authors":"Aida Kamalian, Siavash Shirzadeh Barough, Sara G Ho, Marilyn Albert, Mark G Luciano, Sevil Yasar, Abhay Moghekar","doi":"10.1186/s12987-024-00561-5","DOIUrl":null,"url":null,"abstract":"<p><p>Given the persistent challenge of differentiating idiopathic Normal Pressure Hydrocephalus (iNPH) from similar clinical entities, we conducted an in-depth proteomic study of cerebrospinal fluid (CSF) in 28 shunt-responsive iNPH patients, 38 Mild Cognitive Impairment (MCI) due to Alzheimer's disease, and 49 healthy controls. Utilizing the Olink Explore 3072 panel, we identified distinct proteomic profiles in iNPH that highlight significant downregulation of synaptic markers and cell-cell adhesion proteins. Alongside vimentin and inflammatory markers upregulation, these results suggest ependymal layer and transependymal flow dysfunction. Moreover, downregulation of multiple proteins associated with congenital hydrocephalus (e.g., L1CAM, PCDH9, ISLR2, ADAMTSL2, and B4GAT1) points to a possible shared molecular foundation between congenital hydrocephalus and iNPH. Through orthogonal partial least squares discriminant analysis (OPLS-DA), a panel comprising 13 proteins has been identified as potential diagnostic biomarkers of iNPH, pending external validation. These findings offer novel insights into the pathophysiology of iNPH, with implications for improved diagnosis.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"21 1","pages":"64"},"PeriodicalIF":5.9000,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11312837/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Fluids and Barriers of the CNS","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12987-024-00561-5","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0

Abstract

Given the persistent challenge of differentiating idiopathic Normal Pressure Hydrocephalus (iNPH) from similar clinical entities, we conducted an in-depth proteomic study of cerebrospinal fluid (CSF) in 28 shunt-responsive iNPH patients, 38 Mild Cognitive Impairment (MCI) due to Alzheimer's disease, and 49 healthy controls. Utilizing the Olink Explore 3072 panel, we identified distinct proteomic profiles in iNPH that highlight significant downregulation of synaptic markers and cell-cell adhesion proteins. Alongside vimentin and inflammatory markers upregulation, these results suggest ependymal layer and transependymal flow dysfunction. Moreover, downregulation of multiple proteins associated with congenital hydrocephalus (e.g., L1CAM, PCDH9, ISLR2, ADAMTSL2, and B4GAT1) points to a possible shared molecular foundation between congenital hydrocephalus and iNPH. Through orthogonal partial least squares discriminant analysis (OPLS-DA), a panel comprising 13 proteins has been identified as potential diagnostic biomarkers of iNPH, pending external validation. These findings offer novel insights into the pathophysiology of iNPH, with implications for improved diagnosis.

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
正常压力脑积水的分子特征:脑脊液的大规模蛋白质组分析。
鉴于区分特发性正常压力脑积水(iNPH)与类似临床实体一直是个难题,我们对 28 例分流反应型 iNPH 患者、38 例阿尔茨海默病引起的轻度认知功能障碍(MCI)患者和 49 例健康对照者的脑脊液(CSF)进行了深入的蛋白质组学研究。利用 Olink Explore 3072 面板,我们发现了 iNPH 中独特的蛋白质组特征,突触标记物和细胞-细胞粘附蛋白显著下调。除了波形蛋白和炎症标志物上调外,这些结果表明内膜层和跨内膜流动功能障碍。此外,与先天性脑积水相关的多种蛋白(如 L1CAM、PCDH9、ISLR2、ADAMTSL2 和 B4GAT1)的下调表明先天性脑积水和 iNPH 之间可能存在共同的分子基础。通过正交偏最小二乘法判别分析(OPLS-DA),一个由 13 个蛋白质组成的小组被确定为 iNPH 的潜在诊断生物标记物,目前正在等待外部验证。这些发现为 iNPH 的病理生理学提供了新的见解,对改进诊断具有重要意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Fluids and Barriers of the CNS
Fluids and Barriers of the CNS Neuroscience-Developmental Neuroscience
CiteScore
10.70
自引率
8.20%
发文量
94
审稿时长
14 weeks
期刊介绍: "Fluids and Barriers of the CNS" is a scholarly open access journal that specializes in the intricate world of the central nervous system's fluids and barriers, which are pivotal for the health and well-being of the human body. This journal is a peer-reviewed platform that welcomes research manuscripts exploring the full spectrum of CNS fluids and barriers, with a particular focus on their roles in both health and disease. At the heart of this journal's interest is the cerebrospinal fluid (CSF), a vital fluid that circulates within the brain and spinal cord, playing a multifaceted role in the normal functioning of the brain and in various neurological conditions. The journal delves into the composition, circulation, and absorption of CSF, as well as its relationship with the parenchymal interstitial fluid and the neurovascular unit at the blood-brain barrier (BBB).
期刊最新文献
VIEshunt: towards a ventricular intelligent and electromechanical shunt for hydrocephalus therapy. Hypoxemia exerts detrimental effects on the choroid plexuses and cerebrospinal fluid system in rats. Ventriculosagittal sinus shunt for treating hydrocephalus with elevated cerebrospinal fluid protein. A review of cerebrospinal fluid circulation with respect to Chiari-like malformation and syringomyelia in brachycephalic dogs. Applying machine learning to high-dimensional proteomics datasets for the identification of Alzheimer's disease biomarkers.
×
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