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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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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (82nd percentile)
  • Average Attention Score compared to outputs of the same age and source

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Citations

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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.

X Demographics

X Demographics

The data shown below were collected from the profile of 1 X user 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 55 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Russia 1 2%
Unknown 54 98%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 14 25%
Researcher 12 22%
Student > Ph. D. Student 7 13%
Student > Master 6 11%
Student > Doctoral Student 2 4%
Other 5 9%
Unknown 9 16%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 14 25%
Neuroscience 13 24%
Agricultural and Biological Sciences 7 13%
Medicine and Dentistry 3 5%
Chemistry 2 4%
Other 4 7%
Unknown 12 22%
Attention Score in Context

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
#3,200,780
of 22,832,057 outputs
Outputs from Acta Neuropathologica Communications
#702
of 1,375 outputs
Outputs of similar age
#47,990
of 285,322 outputs
Outputs of similar age from Acta Neuropathologica Communications
#13
of 26 outputs
Altmetric has tracked 22,832,057 research outputs across all sources so far. Compared to these this one has done well and is in the 85th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,375 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.9. 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 285,322 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 82% 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 is in the 42nd percentile – i.e., 42% of its contemporaries scored the same or lower than it.