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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
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (89th percentile)
  • Good Attention Score compared to outputs of the same age and source (68th percentile)

Mentioned by

news
1 news outlet
twitter
11 tweeters

Citations

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72 Dimensions

Readers on

mendeley
152 Mendeley
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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 152 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 147 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 35 23%
Researcher 32 21%
Student > Master 26 17%
Student > Bachelor 13 9%
Other 7 5%
Other 20 13%
Unknown 19 13%
Readers by discipline Count As %
Agricultural and Biological Sciences 27 18%
Neuroscience 27 18%
Biochemistry, Genetics and Molecular Biology 26 17%
Medicine and Dentistry 21 14%
Pharmacology, Toxicology and Pharmaceutical Science 8 5%
Other 18 12%
Unknown 25 16%

Attention Score in Context

This research output has an Altmetric Attention Score of 13. 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
#1,127,810
of 13,255,689 outputs
Outputs from Molecular Neurodegeneration
#74
of 564 outputs
Outputs of similar age
#36,739
of 354,619 outputs
Outputs of similar age from Molecular Neurodegeneration
#12
of 47 outputs
Altmetric has tracked 13,255,689 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 564 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.5. This one has done well, scoring higher than 85% 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 354,619 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 89% of its contemporaries.
We're also able to compare this research output to 47 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 68% of its contemporaries.