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Trisomy of human chromosome 21 enhances amyloid-β deposition independently of an extra copy of APP

Overview of attention for article published in Brain, June 2018
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • Among the highest-scoring outputs from this source (#33 of 7,604)
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (98th percentile)

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204 Mendeley
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Title
Trisomy of human chromosome 21 enhances amyloid-β deposition independently of an extra copy of APP
Published in
Brain, June 2018
DOI 10.1093/brain/awy159
Pubmed ID
Authors

Frances K Wiseman, Laura J Pulford, Chris Barkus, Fan Liao, Erik Portelius, Robin Webb, Lucia Chávez-Gutiérrez, Karen Cleverley, Sue Noy, Olivia Sheppard, Toby Collins, Caroline Powell, Claire J Sarell, Matthew Rickman, Xun Choong, Justin L Tosh, Carlos Siganporia, Heather T Whittaker, Floy Stewart, Maria Szaruga, Michael P Murphy, Kaj Blennow, Bart de Strooper, Henrik Zetterberg, David Bannerman, David M Holtzman, Victor L J Tybulewicz, Elizabeth M C Fisher, Andre Strydom, Elizabeth Fisher, Dean Nizetic, John Hardy, Victor Tybulewicz, Annette Karmiloff-Smith

Abstract

Down syndrome, caused by trisomy of chromosome 21, is the single most common risk factor for early-onset Alzheimer's disease. Worldwide approximately 6 million people have Down syndrome, and all these individuals will develop the hallmark amyloid plaques and neurofibrillary tangles of Alzheimer's disease by the age of 40 and the vast majority will go on to develop dementia. Triplication of APP, a gene on chromosome 21, is sufficient to cause early-onset Alzheimer's disease in the absence of Down syndrome. However, whether triplication of other chromosome 21 genes influences disease pathogenesis in the context of Down syndrome is unclear. Here we show, in a mouse model, that triplication of chromosome 21 genes other than APP increases amyloid-β aggregation, deposition of amyloid-β plaques and worsens associated cognitive deficits. This indicates that triplication of chromosome 21 genes other than APP is likely to have an important role to play in Alzheimer's disease pathogenesis in individuals who have Down syndrome. We go on to show that the effect of trisomy of chromosome 21 on amyloid-β aggregation correlates with an unexpected shift in soluble amyloid-β 40/42 ratio. This alteration in amyloid-β isoform ratio occurs independently of a change in the carboxypeptidase activity of the γ-secretase complex, which cleaves the peptide from APP, or the rate of extracellular clearance of amyloid-β. These new mechanistic insights into the role of triplication of genes on chromosome 21, other than APP, in the development of Alzheimer's disease in individuals who have Down syndrome may have implications for the treatment of this common cause of neurodegeneration.

X Demographics

X Demographics

The data shown below were collected from the profiles of 90 X users 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 204 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 204 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 41 20%
Student > Bachelor 35 17%
Researcher 23 11%
Student > Master 15 7%
Professor 9 4%
Other 25 12%
Unknown 56 27%
Readers by discipline Count As %
Neuroscience 43 21%
Biochemistry, Genetics and Molecular Biology 34 17%
Agricultural and Biological Sciences 17 8%
Medicine and Dentistry 14 7%
Pharmacology, Toxicology and Pharmaceutical Science 6 3%
Other 22 11%
Unknown 68 33%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 676. 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 24 September 2019.
All research outputs
#31,207
of 25,402,889 outputs
Outputs from Brain
#33
of 7,604 outputs
Outputs of similar age
#625
of 342,645 outputs
Outputs of similar age from Brain
#2
of 76 outputs
Altmetric has tracked 25,402,889 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 7,604 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 27.8. This one has done particularly well, scoring higher than 99% 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 342,645 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 99% of its contemporaries.
We're also able to compare this research output to 76 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 98% of its contemporaries.