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An integrative genome-wide transcriptome reveals that candesartan is neuroprotective and a candidate therapeutic for Alzheimer’s disease

Overview of attention for article published in Alzheimer's Research & Therapy, January 2016
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • Among the highest-scoring outputs from this source (#19 of 1,309)
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (99th percentile)

Mentioned by

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27 news outlets
blogs
5 blogs
twitter
17 X users
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2 Facebook pages

Citations

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35 Dimensions

Readers on

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75 Mendeley
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Title
An integrative genome-wide transcriptome reveals that candesartan is neuroprotective and a candidate therapeutic for Alzheimer’s disease
Published in
Alzheimer's Research & Therapy, January 2016
DOI 10.1186/s13195-015-0167-5
Pubmed ID
Authors

Abdel G. Elkahloun, Roman Hafko, Juan M. Saavedra

Abstract

Alzheimer's disease is the most frequent age-related dementia, and is currently without treatment. To identify possible targets for early therapeutic intervention we focused on glutamate excitotoxicity, a major early pathogenic factor, and the effects of candesartan, an angiotensin receptor blocker of neuroprotective efficacy in cell cultures and rodent models of Alzheimer's disease. The overall goal of the study was to determine whether gene analysis of drug effects in a primary neuronal culture correlate with alterations in gene expression in Alzheimer's disease, thus providing further preclinical evidence of beneficial therapeutic effects. Primary neuronal cultures were treated with candesartan at neuroprotective concentrations followed by excitotoxic glutamate amounts. We performed genome-wide expression profile analysis and data evaluation by ingenuity pathway analysis and gene set enrichment analysis, compared with alterations in gene expression from two independent published datasets identified by microarray analysis of postmortem hippocampus from Alzheimer's disease patients. Preferential expression in cerebrovascular endothelial cells or neurons was analyzed by comparison to published gene expression in these cells isolated from human cortex by laser capture microdissection. Candesartan prevented glutamate upregulation or downregulation of several hundred genes in our cultures. Ingenuity pathway analysis and gene set enrichment analysis revealed that inflammation, cardiovascular disease and diabetes signal transduction pathways and amyloid β metabolism were major components of the neuronal response to glutamate excitotoxicity. Further analysis showed associations of glutamate-induced changes in the expression of several hundred genes, normalized by candesartan, with similar alterations observed in hippocampus from Alzheimer's disease patients. Gene analysis of neurons and cerebrovascular endothelial cells obtained by laser capture microdissection revealed that genes up- and downregulated by glutamate were preferentially expressed in endothelial cells and neurons, respectively. Our data may be interpreted as evidence of direct candesartan neuroprotection beyond its effects on blood pressure, revealing common and novel disease mechanisms that may underlie the in vitro gene alterations reported here and glutamate-induced cell injury in Alzheimer's disease. Our observations provide novel evidence for candesartan neuroprotection through early molecular mechanisms of injury in Alzheimer's disease, supporting testing this compound in controlled clinical studies in the early stages of the illness.

X Demographics

X Demographics

The data shown below were collected from the profiles of 17 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 75 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 75 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 14 19%
Researcher 11 15%
Student > Ph. D. Student 11 15%
Student > Bachelor 7 9%
Other 4 5%
Other 13 17%
Unknown 15 20%
Readers by discipline Count As %
Medicine and Dentistry 8 11%
Neuroscience 8 11%
Biochemistry, Genetics and Molecular Biology 7 9%
Agricultural and Biological Sciences 7 9%
Psychology 6 8%
Other 18 24%
Unknown 21 28%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 246. 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 April 2016.
All research outputs
#135,446
of 23,767,404 outputs
Outputs from Alzheimer's Research & Therapy
#19
of 1,309 outputs
Outputs of similar age
#2,463
of 400,575 outputs
Outputs of similar age from Alzheimer's Research & Therapy
#1
of 18 outputs
Altmetric has tracked 23,767,404 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,309 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 26.9. This one has done particularly well, scoring higher than 98% 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 400,575 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 99% of its contemporaries.
We're also able to compare this research output to 18 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 99% of its contemporaries.