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The A673T mutation in the amyloid precursor protein reduces the production of β-amyloid protein from its β-carboxyl terminal fragment in cells

Overview of attention for article published in Acta Neuropathologica Communications, November 2015
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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 (83rd percentile)
  • Average Attention Score compared to outputs of the same age and source

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1 news outlet
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1 tweeter

Citations

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14 Dimensions

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49 Mendeley
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Title
The A673T mutation in the amyloid precursor protein reduces the production of β-amyloid protein from its β-carboxyl terminal fragment in cells
Published in
Acta Neuropathologica Communications, November 2015
DOI 10.1186/s40478-015-0247-6
Pubmed ID
Authors

Asuka Kokawa, Seiko Ishihara, Hitomi Fujiwara, Mika Nobuhara, Minori Iwata, Yasuo Ihara, Satoru Funamoto

Abstract

The A673T mutation in the amyloid precursor protein (APP) protects against Alzheimer's disease by reducing β-amyloid protein (Aβ) production. This mutation reduced the release of the soluble APP fragment (sAPPβ), which is processed by β-secretase, suggesting a concomitant decrease in the β-carboxyl fragment of APP (C99), which is a direct substrate of γ-secretase for Aβ production. However, it remains controversial whether the level of C99 is significantly reduced in cells expressing APP that carry A673T as the cause of reduced Aβ production. Here, we investigated the effect of the A673T mutation in C99 on γ-cleavage in cells. We found that the level of C99 in cells expressing APP A673T was indistinctive of that observed in cells expressing wild-type APP, although the release of sAPPβ was significantly reduced in the APP A673T cells. In addition, our reconstituted β-secretase assay demonstrated no significant difference in β-cleavage on an APP fragment carrying the A673T mutation compared with the wild-type fragment. Importantly, cells expressing C99 containing the A673T mutation (C99 A2T; in accordance with the Aβ numbering) produced roughly half the level of Aβ compared with the wild-type C99, suggesting that the C99 A2T is an insufficient substrate of γ-secretase in cells. A cell-free γ-secretase assay revealed that Aβ production from the microsomal fraction of cells expressing C99 A2T was diminished. A sucrose gradient centrifugation analysis indicated that the levels of the C99 A2T that was codistributed with γ-secretase components in the raft fractions were reduced significantly. Our data indicate that the A673T mutation in APP alters the release of sAPPβ, but not the C99 level, and that the C99 A2T is an inefficient substrate for γ-secretase in cell-based assay.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter 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 49 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Russia 1 2%
Unknown 48 98%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 12 24%
Researcher 10 20%
Student > Ph. D. Student 8 16%
Student > Master 6 12%
Student > Doctoral Student 2 4%
Other 4 8%
Unknown 7 14%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 14 29%
Neuroscience 10 20%
Agricultural and Biological Sciences 7 14%
Medicine and Dentistry 4 8%
Pharmacology, Toxicology and Pharmaceutical Science 1 2%
Other 4 8%
Unknown 9 18%

Attention Score in Context

This research output has an Altmetric Attention Score of 10. 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 29 May 2016.
All research outputs
#2,685,466
of 19,556,424 outputs
Outputs from Acta Neuropathologica Communications
#605
of 1,176 outputs
Outputs of similar age
#49,489
of 298,369 outputs
Outputs of similar age from Acta Neuropathologica Communications
#41
of 82 outputs
Altmetric has tracked 19,556,424 research outputs across all sources so far. Compared to these this one has done well and is in the 86th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,176 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.0. This one is in the 46th percentile – i.e., 46% of its peers scored the same or lower than it.
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 298,369 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 83% of its contemporaries.
We're also able to compare this research output to 82 others from the same source and published within six weeks on either side of this one. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.