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HMGB1 and thrombin mediate the blood-brain barrier dysfunction acting as biomarkers of neuroinflammation and progression to neurodegeneration in Alzheimer's disease.

Overview of attention for article published in Journal of Neuroinflammation, August 2016
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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 (88th percentile)
  • High Attention Score compared to outputs of the same age and source (89th percentile)

Mentioned by

news
1 news outlet
twitter
3 tweeters
wikipedia
1 Wikipedia page

Readers on

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33 Mendeley
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Title
HMGB1 and thrombin mediate the blood-brain barrier dysfunction acting as biomarkers of neuroinflammation and progression to neurodegeneration in Alzheimer's disease.
Published in
Journal of Neuroinflammation, August 2016
DOI 10.1186/s12974-016-0670-z
Pubmed ID
Authors

Festoff, Barry W, Sajja, Ravi K, van Dreden, Patrick, Cucullo, Luca, Barry W. Festoff, Ravi K. Sajja, Patrick van Dreden, Luca Cucullo

Abstract

The blood-brain barrier (BBB) dysfunction represents an early feature of Alzheimer's disease (AD) that precedes the hallmarks of amyloid beta (amyloid β) plaque deposition and neuronal neurofibrillary tangle (NFT) formation. A damaged BBB correlates directly with neuroinflammation involving microglial activation and reactive astrogliosis, which is associated with increased expression and/or release of high-mobility group box protein 1 (HMGB1) and thrombin. However, the link between the presence of these molecules, BBB damage, and progression to neurodegeneration in AD is still elusive. Therefore, we aimed to profile and validate non-invasive clinical biomarkers of BBB dysfunction and neuroinflammation to assess the progression to neurodegeneration in mild cognitive impairment (MCI) and AD patients. We determined the serum levels of various proinflammatory damage-associated molecules in aged control subjects and patients with MCI or AD using validated ELISA kits. We then assessed the specific and direct effects of such molecules on BBB integrity in vitro using human primary brain microvascular endothelial cells or a cell line. We observed a significant increase in serum HMGB1 and soluble receptor for advanced glycation end products (sRAGE) that correlated well with amyloid beta levels in AD patients (vs. control subjects). Interestingly, serum HMGB1 levels were significantly elevated in MCI patients compared to controls or AD patients. In addition, as a marker of BBB damage, soluble thrombomodulin (sTM) antigen, and activity were significantly (and distinctly) increased in MCI and AD patients. Direct in vitro BBB integrity assessment further revealed a significant and concentration-dependent increase in paracellular permeability to dextrans by HMGB1 or α-thrombin, possibly through disruption of zona occludins-1 bands. Pre-treatment with anti-HMGB1 monoclonal antibody blocked HMGB1 effects and leaving BBB integrity intact. Our current studies indicate that thrombin and HMGB1 are causal proximate proinflammatory mediators of BBB dysfunction, while sTM levels may indicate BBB endothelial damage; HMGB1 and sRAGE might serve as clinical biomarkers for progression and/or therapeutic efficacy along the AD spectrum.

Twitter Demographics

The data shown below were collected from the profiles of 3 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 33 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 3%
Brazil 1 3%
United States 1 3%
Unknown 30 91%

Demographic breakdown

Readers by professional status Count As %
Student > Master 11 33%
Student > Ph. D. Student 7 21%
Researcher 7 21%
Student > Bachelor 3 9%
Student > Postgraduate 2 6%
Other 3 9%
Readers by discipline Count As %
Neuroscience 8 24%
Agricultural and Biological Sciences 7 21%
Medicine and Dentistry 6 18%
Biochemistry, Genetics and Molecular Biology 5 15%
Veterinary Science and Veterinary Medicine 1 3%
Other 6 18%

Attention Score in Context

This research output has an Altmetric Attention Score of 14. 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 03 May 2018.
All research outputs
#777,196
of 9,792,785 outputs
Outputs from Journal of Neuroinflammation
#63
of 1,249 outputs
Outputs of similar age
#30,970
of 259,565 outputs
Outputs of similar age from Journal of Neuroinflammation
#6
of 56 outputs
Altmetric has tracked 9,792,785 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 92nd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,249 research outputs from this source. They receive a mean Attention Score of 4.8. This one has done particularly well, scoring higher than 94% 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 259,565 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 88% of its contemporaries.
We're also able to compare this research output to 56 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 89% of its contemporaries.