首页 | 本学科首页   官方微博 | 高级检索  
     


Identification of novel CSF biomarkers for neurodegeneration and their validation by a high-throughput multiplexed targeted proteomic assay
Authors:Wendy?E.?Heywood,Daniela?Galimberti,Emily?Bliss,Ernestas?Sirka,Ross?W.?Paterson,Nadia?K.?Magdalinou,Miryam?Carecchio,Emma?Reid,Amanda?Heslegrave,Chiara?Fenoglio,Elio?Scarpini,Jonathan?M.?Schott,Nick?C.?Fox,John?Hardy,Kailash?Bahtia,Simon?Heales,Neil?J.?Sebire,Henrik?Zetterburg,Kevin?Mills  author-information"  >  author-information__contact u-icon-before"  >  mailto:kevin.mills@ucl.ac.uk"   title="  kevin.mills@ucl.ac.uk"   itemprop="  email"   data-track="  click"   data-track-action="  Email author"   data-track-label="  "  >Email author
Affiliation:1.Centre for Translational Omics, University College London Institute of Child Health,London,UK;2.Neurology Unit, Department of Pathophysiology and Transplantation,University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico,Milan,Italy;3.Dementia Research Centre, University College London Institute of Neurology,London,UK;4.Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology,London,UK;5.Neuropediatrics Unit, IRCCS Istituto Neurologico Carlo Besta,Milan,Italy;6.Great Ormond Street Hospital for Children,London,UK;7.Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,The Sahlgrenska Academy, University of Gothenburg,M?lndal,Sweden
Abstract:

Background

Currently there are no effective treatments for many neurodegenerative diseases. Reliable biomarkers for identifying and stratifying these diseases will be important in the development of future novel therapies. Lewy Body Dementia (LBD) is considered an under diagnosed form of dementia for which markers are needed to discriminate LBD from other forms of dementia such as Alzheimer’s Disease (AD). This work describes a Label-Free proteomic profiling analysis of cerebral spinal fluid (CSF) from non-neurodegenerative controls and patients with LBD. Using this technology we identified several potential novel markers for LBD. These were then combined with other biomarkers from previously published studies, to create a 10 min multiplexed targeted and translational MRM-LC-MS/MS assay. This test was used to validate our new assay in a larger cohort of samples including controls and the other neurodegenerative conditions of Alzheimer’s and Parkinson’s disease (PD).

Results

Thirty eight proteins showed significantly (p?p?p?p?p?2?activator protein, and prosaposin). Protein-DJ1 was only elevated significantly in the PD group and not in either LBD or AD samples. Correlations with Alzheimer-associated amyloid β-42 levels, determined by ELISA, were observed for transthyretin, GM2 activator protein and IGF2 in the AD disease group (r2?≥?0.39, p?≤?0.012). Cystatin C, ubiquitin and osteopontin showed a strong significant linear relationship (r2?≥?0.4, p?≤?0.03) with phosphorylated–tau levels in all groups, whilst malate dehydrogenase and apolipoprotein E demonstrated a linear relationship with phosphorylated-tau and total-tau levels in only AD and LBD disease groups.

Conclusions

Using proteomics we have identified several potential and novel markers of neurodegeneration and subsequently validated them using a rapid, multiplexed mass spectral test. This targeted proteomic platform can measure common markers of neurodegeneration that correlate with existing diagnostic makers as well as some that have potential to show changes between AD from LBD.
Keywords:
本文献已被 SpringerLink 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号