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Murine versus human apolipoprotein E4: differential facilitation of and co-localization in cerebral amyloid angiopathy and amyloid plaques in APP transgenic mouse models

Overview of attention for article published in Acta Neuropathologica Communications, 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 (87th percentile)
  • High Attention Score compared to outputs of the same age and source (80th percentile)

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1 news outlet
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1 patent

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Title
Murine versus human apolipoprotein E4: differential facilitation of and co-localization in cerebral amyloid angiopathy and amyloid plaques in APP transgenic mouse models
Published in
Acta Neuropathologica Communications, November 2015
DOI 10.1186/s40478-015-0250-y
Pubmed ID
Authors

Fan Liao, Tony J. Zhang, Hong Jiang, Katheryn B. Lefton, Grace O. Robinson, Robert Vassar, Patrick M. Sullivan, David M. Holtzman

Abstract

Amyloid β (Aβ) accumulates in the extracellular space as diffuse and neuritic plaques in Alzheimer's disease (AD). Aβ also deposits on the walls of arterioles as cerebral amyloid angiopathy (CAA) in most cases of AD and sometimes independently of AD. Apolipoprotein E (apoE) ɛ4 is associated with increases in both Aβ plaques and CAA in humans. Studies in mouse models that develop Aβ deposition have shown that murine apoE and human apoE4 have different abilities to facilitate plaque or CAA formation when studied independently. To better understand and compare the effects of murine apoE and human apoE4, we bred 5XFAD (line 7031) transgenic mice so that they expressed one copy of murine apoE and one copy of human apoE4 under the control of the normal murine apoE regulatory elements (5XFAD/apoE(m/4)). The 5XFAD/apoE(m/4) mice contained levels of parenchymal CAA that were intermediate between 5XFAD/apoE(m/m) and 5XFAD/apoE(4/4) mice. In 5XFAD/apoE(m/4) mice, we found that Aβ parenchymal plaques co-localized with much more apoE than did parenchymal CAA, suggesting differential co-aggregation of apoE with Aβ in plaques versus CAA. More importantly, within the brain parenchyma of the 5XFAD/apoE(m/4) mice, plaques contained more murine apoE, which on its own results in more pronounced and earlier plaque formation, while CAA contained more human apoE4 which on its own results in more pronounced CAA formation. We further confirmed the co-aggregation of mouse apoE with Aβ in plaques by showing a strong correlation between insoluble mouse apoE and insoluble Aβ in PS1APP-21/apoE(m/4) mice which develop plaques without CAA. These studies suggest that both murine apoE and human apoE4 facilitate differential opposing effects in influencing Aβ plaques versus CAA via different co-aggregation with these two amyloid lesions and set the stage for understanding these effects at a molecular level.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 83 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 83 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 20 24%
Researcher 12 14%
Student > Bachelor 9 11%
Student > Master 7 8%
Student > Doctoral Student 6 7%
Other 15 18%
Unknown 14 17%
Readers by discipline Count As %
Neuroscience 27 33%
Agricultural and Biological Sciences 9 11%
Medicine and Dentistry 6 7%
Biochemistry, Genetics and Molecular Biology 5 6%
Pharmacology, Toxicology and Pharmaceutical Science 5 6%
Other 14 17%
Unknown 17 20%
Attention Score in Context

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 15 August 2023.
All research outputs
#2,500,638
of 24,293,076 outputs
Outputs from Acta Neuropathologica Communications
#416
of 1,488 outputs
Outputs of similar age
#35,441
of 287,853 outputs
Outputs of similar age from Acta Neuropathologica Communications
#6
of 26 outputs
Altmetric has tracked 24,293,076 research outputs across all sources so far. Compared to these this one has done well and is in the 89th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,488 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 13.4. This one has gotten more attention than average, scoring higher than 71% 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 287,853 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 87% of its contemporaries.
We're also able to compare this research output to 26 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 80% of its contemporaries.