↓ Skip to main content

Identification of novel CSF biomarkers for neurodegeneration and their validation by a high-throughput multiplexed targeted proteomic assay

Overview of attention for article published in Molecular Neurodegeneration, December 2015
Altmetric Badge

About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (90th percentile)
  • High Attention Score compared to outputs of the same age and source (80th percentile)

Mentioned by

news
1 news outlet
twitter
11 tweeters

Citations

dimensions_citation
82 Dimensions

Readers on

mendeley
165 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Identification of novel CSF biomarkers for neurodegeneration and their validation by a high-throughput multiplexed targeted proteomic assay
Published in
Molecular Neurodegeneration, December 2015
DOI 10.1186/s13024-015-0059-y
Pubmed ID
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

Abstract

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). Thirty eight proteins showed significantly (p < 0.05) altered expression in LBD CSF by proteomic profiling. The targeted MRM-LC-MS/MS assay revealed 4 proteins that were specific for the identification of AD from LBD: ectonucleotide pyrophosphatase/phosphodiesterase 2 (p < 0.0001), lysosome-associated membrane protein 1 (p < 0.0001), pro-orexin (p < 0.0017) and transthyretin (p < 0.0001). Nineteen proteins were elevated significantly in both AD and LBD versus the control group of which 4 proteins are novel (malate dehydrogenase 1, serum amyloid A4, GM2-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 (r(2) ≥ 0.39, p ≤ 0.012). Cystatin C, ubiquitin and osteopontin showed a strong significant linear relationship (r(2) ≥ 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. 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.

Twitter Demographics

The data shown below were collected from the profiles of 11 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 165 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
France 1 <1%
United Kingdom 1 <1%
Russia 1 <1%
Spain 1 <1%
United States 1 <1%
Unknown 160 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 36 22%
Researcher 33 20%
Student > Master 28 17%
Student > Bachelor 15 9%
Other 8 5%
Other 23 14%
Unknown 22 13%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 29 18%
Agricultural and Biological Sciences 29 18%
Neuroscience 26 16%
Medicine and Dentistry 26 16%
Pharmacology, Toxicology and Pharmaceutical Science 7 4%
Other 20 12%
Unknown 28 17%

Attention Score in Context

This research output has an Altmetric Attention Score of 15. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 August 2016.
All research outputs
#1,574,690
of 17,803,527 outputs
Outputs from Molecular Neurodegeneration
#116
of 698 outputs
Outputs of similar age
#37,373
of 375,853 outputs
Outputs of similar age from Molecular Neurodegeneration
#12
of 57 outputs
Altmetric has tracked 17,803,527 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 91st percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 698 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.6. This one has done well, scoring higher than 83% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 375,853 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 90% of its contemporaries.
We're also able to compare this research output to 57 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 80% of its contemporaries.