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Glymphatic distribution of CSF-derived apoE into brain is isoform specific and suppressed during sleep deprivation

Overview of attention for article published in Molecular Neurodegeneration, December 2016
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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 (85th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (61st percentile)

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1 news outlet
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4 tweeters

Citations

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90 Dimensions

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158 Mendeley
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Title
Glymphatic distribution of CSF-derived apoE into brain is isoform specific and suppressed during sleep deprivation
Published in
Molecular Neurodegeneration, December 2016
DOI 10.1186/s13024-016-0138-8
Pubmed ID
Authors

Thiyagaragan M. Achariyar, Baoman Li, Weiguo Peng, Philip B. Verghese, Yang Shi, Evan McConnell, Abdellatif Benraiss, Tristan Kasper, Wei Song, Takahiro Takano, David M. Holtzman, Maiken Nedergaard, Rashid Deane

Abstract

Apolipoprotein E (apoE) is a major carrier of cholesterol and essential for synaptic plasticity. In brain, it's expressed by many cells but highly expressed by the choroid plexus and the predominant apolipoprotein in cerebrospinal fluid (CSF). The role of apoE in the CSF is unclear. Recently, the glymphatic system was described as a clearance system whereby CSF and ISF (interstitial fluid) is exchanged via the peri-arterial space and convective flow of ISF clearance is mediated by aquaporin 4 (AQP4), a water channel. We reasoned that this system also serves to distribute essential molecules in CSF into brain. The aim was to establish whether apoE in CSF, secreted by the choroid plexus, is distributed into brain, and whether this distribution pattern was altered by sleep deprivation. We used fluorescently labeled lipidated apoE isoforms, lenti-apoE3 delivered to the choroid plexus, immunohistochemistry to map apoE brain distribution, immunolabeled cells and proteins in brain, Western blot analysis and ELISA to determine apoE levels and radiolabeled molecules to quantify CSF inflow into brain and brain clearance in mice. Data were statistically analyzed using ANOVA or Student's t- test. We show that the glymphatic fluid transporting system contributes to the delivery of choroid plexus/CSF-derived human apoE to neurons. CSF-delivered human apoE entered brain via the perivascular space of penetrating arteries and flows radially around arteries, but not veins, in an isoform specific manner (apoE2 > apoE3 > apoE4). Flow of apoE around arteries was facilitated by AQP4, a characteristic feature of the glymphatic system. ApoE3, delivered by lentivirus to the choroid plexus and ependymal layer but not to the parenchymal cells, was present in the CSF, penetrating arteries and neurons. The inflow of CSF, which contains apoE, into brain and its clearance from the interstitium were severely suppressed by sleep deprivation compared to the sleep state. Thus, choroid plexus/CSF provides an additional source of apoE and the glymphatic fluid transporting system delivers it to brain via the periarterial space. By implication, failure in this essential physiological role of the glymphatic fluid flow and ISF clearance may also contribute to apoE isoform-specific disorders in the long term.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 158 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 <1%
Japan 1 <1%
Unknown 156 99%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 25 16%
Researcher 24 15%
Student > Ph. D. Student 23 15%
Student > Master 22 14%
Student > Doctoral Student 13 8%
Other 27 17%
Unknown 24 15%
Readers by discipline Count As %
Neuroscience 39 25%
Medicine and Dentistry 24 15%
Agricultural and Biological Sciences 20 13%
Biochemistry, Genetics and Molecular Biology 14 9%
Pharmacology, Toxicology and Pharmaceutical Science 6 4%
Other 22 14%
Unknown 33 21%

Attention Score in Context

This research output has an Altmetric Attention Score of 12. 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 10 November 2017.
All research outputs
#1,872,644
of 17,094,905 outputs
Outputs from Molecular Neurodegeneration
#196
of 675 outputs
Outputs of similar age
#55,034
of 396,226 outputs
Outputs of similar age from Molecular Neurodegeneration
#24
of 63 outputs
Altmetric has tracked 17,094,905 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 675 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.3. This one has gotten more attention than average, scoring higher than 70% 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 396,226 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 85% of its contemporaries.
We're also able to compare this research output to 63 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 61% of its contemporaries.