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Gene expression and functional annotation of human choroid plexus epithelium failure in Alzheimer’s disease

Overview of attention for article published in BMC Genomics, November 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 (88th percentile)
  • High Attention Score compared to outputs of the same age and source (93rd percentile)

Mentioned by

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1 news outlet
twitter
4 tweeters
patent
1 patent

Citations

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33 Dimensions

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74 Mendeley
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Title
Gene expression and functional annotation of human choroid plexus epithelium failure in Alzheimer’s disease
Published in
BMC Genomics, November 2015
DOI 10.1186/s12864-015-2159-z
Pubmed ID
Authors

Arthur A. Bergen, Sovann Kaing, Jacoline B. ten Brink, Theo G. Gorgels, Sarah F. Janssen

Abstract

Alzheimer's disease (AD) is the most common form of dementia. AD has a multifactorial disease etiology and is currently untreatable. Multiple genes and molecular mechanisms have been implicated in AD, including ß-amyloid deposition in the brain, neurofibrillary tangle accumulation of hyper-phosphorylated Tau, synaptic failure, oxidative stress and inflammation. Relatively little is known about the role of the blood-brain barriers, especially the blood-cerebrospinal fluid barrier (BCSFB), in AD. The BCSFB is involved in cerebrospinal fluid (CSF) production, maintenance of brain homeostasis and neurodegenerative disorders. Using an Agilent platform with common reference design, we performed a large scale gene expression analysis and functional annotation of the Choroid Plexus Epithelium (CPE), which forms the BCSFB. We obtained 2 groups of freshly frozen Choroid Plexus (CP) of 7 human donor brains each, with and without AD: Braak stages (0-1) and (5-6). We cut CP cryo-sections and isolated RNA from cresyl-violet stained, laser dissected CPE cells. Gene expression results were analysed with T-tests (R) and the knowledge-database Ingenuity. We found statistically significantly altered gene expression data sets, biological functions, canonical pathways, molecular networks and functionalities in AD-affected CPE. We observed specific cellular changes due to increased oxidative stress, such as the unfolded protein response, E1F2 and NRF2 signalling and the protein ubiquitin pathway. Most likely, the AD-affected BCSFB barrier becomes more permeable due to downregulation of CLDN5. Finally, our data also predicted down regulation of the glutathione mediated detoxification pathway and the urea cycle in the AD CPE, which suggest that the CPE sink action may be impaired. Remarkably, the expression of a number of genes known to be involved in AD, such as APP, PSEN1, PSEN2, TTR and CLU is moderate to high and remains stable in both healthy and affected CPE. Literature labelling of our new functional molecular networks confirmed multiple previous (molecular) observations in the AD literature and revealed many new ones. We conclude that CPE failure in AD exists. Combining our data with those of the literature, we propose the following chronological and overlapping chain of events: increased Aß burden on CPE; increased oxidative stress in CPE; despite continuous high expression of TTR: decreased capability of CPE to process amyloid; (pro-) inflammatory and growth factor signalling by CPE; intracellular ubiquitin involvement, remodelling of CPE tight junctions and, finally, cellular atrophy. Our data corroborates the hypothesis that increased BCSFB permeability, especially loss of selective CLDN5-mediated paracellular transport, altered CSF production and CPE sink action, as well as loss of CPE mediated macrophage recruitment contribute to the pathogenesis of AD.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 74 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Netherlands 1 1%
Sweden 1 1%
Unknown 72 97%

Demographic breakdown

Readers by professional status Count As %
Researcher 14 19%
Student > Ph. D. Student 12 16%
Student > Master 11 15%
Student > Bachelor 7 9%
Student > Doctoral Student 5 7%
Other 17 23%
Unknown 8 11%
Readers by discipline Count As %
Neuroscience 17 23%
Medicine and Dentistry 15 20%
Biochemistry, Genetics and Molecular Biology 8 11%
Agricultural and Biological Sciences 7 9%
Pharmacology, Toxicology and Pharmaceutical Science 5 7%
Other 8 11%
Unknown 14 19%

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 15 April 2021.
All research outputs
#1,701,612
of 18,217,940 outputs
Outputs from BMC Genomics
#555
of 9,550 outputs
Outputs of similar age
#28,165
of 243,410 outputs
Outputs of similar age from BMC Genomics
#62
of 996 outputs
Altmetric has tracked 18,217,940 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 9,550 research outputs from this source. They receive a mean Attention Score of 4.4. 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 243,410 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 996 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 93% of its contemporaries.