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Efficient clearance of Aβ protofibrils in AβPP-transgenic mice treated with a brain-penetrating bifunctional antibody

Overview of attention for article published in Alzheimer's Research & Therapy, May 2018
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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 (87th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (52nd percentile)

Mentioned by

news
1 news outlet
blogs
1 blog
twitter
1 X user
patent
2 patents

Citations

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51 Dimensions

Readers on

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89 Mendeley
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Title
Efficient clearance of Aβ protofibrils in AβPP-transgenic mice treated with a brain-penetrating bifunctional antibody
Published in
Alzheimer's Research & Therapy, May 2018
DOI 10.1186/s13195-018-0377-8
Pubmed ID
Authors

Stina Syvänen, Greta Hultqvist, Tobias Gustavsson, Astrid Gumucio, Hanna Laudon, Linda Söderberg, Martin Ingelsson, Lars Lannfelt, Dag Sehlin

Abstract

Amyloid-β (Aβ) immunotherapy is one of the most promising disease-modifying strategies for Alzheimer's disease (AD). Despite recent progress targeting aggregated forms of Aβ, low antibody brain penetrance remains a challenge. In the present study, we used transferrin receptor (TfR)-mediated transcytosis to facilitate brain uptake of our previously developed Aβ protofibril-selective mAb158, with the aim of increasing the efficacy of immunotherapy directed toward soluble Aβ protofibrils. Aβ protein precursor (AβPP)-transgenic mice (tg-ArcSwe) were given a single dose of mAb158, modified for TfR-mediated transcytosis (RmAb158-scFv8D3), in comparison with an equimolar dose or a tenfold higher dose of unmodified recombinant mAb158 (RmAb158). Soluble Aβ protofibrils and total Aβ in the brain were measured by enzyme-linked immunosorbent assay (ELISA). Brain distribution of radiolabeled antibodies was visualized by positron emission tomography (PET) and ex vivo autoradiography. ELISA analysis of Tris-buffered saline brain extracts demonstrated a 40% reduction of soluble Aβ protofibrils in both RmAb158-scFv8D3- and high-dose RmAb158-treated mice, whereas there was no Aβ protofibril reduction in mice treated with a low dose of RmAb158. Further, ex vivo autoradiography and PET imaging revealed different brain distribution patterns of RmAb158-scFv8D3 and RmAb158, suggesting that these antibodies may affect Aβ levels by different mechanisms. With a combination of biochemical and imaging analyses, this study demonstrates that antibodies engineered to be transported across the blood-brain barrier can be used to increase the efficacy of Aβ immunotherapy. This strategy may allow for decreased antibody doses and thereby reduced side effects and treatment costs.

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 89 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 89 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 19 21%
Student > Bachelor 11 12%
Student > Master 9 10%
Student > Ph. D. Student 8 9%
Professor 4 4%
Other 17 19%
Unknown 21 24%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 13 15%
Agricultural and Biological Sciences 10 11%
Pharmacology, Toxicology and Pharmaceutical Science 10 11%
Neuroscience 6 7%
Medicine and Dentistry 5 6%
Other 16 18%
Unknown 29 33%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 18. 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 14 February 2024.
All research outputs
#2,023,977
of 25,365,817 outputs
Outputs from Alzheimer's Research & Therapy
#370
of 1,452 outputs
Outputs of similar age
#41,242
of 337,527 outputs
Outputs of similar age from Alzheimer's Research & Therapy
#13
of 25 outputs
Altmetric has tracked 25,365,817 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 92nd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,452 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 26.6. This one has gotten more attention than average, scoring higher than 74% 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 337,527 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 25 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 52% of its contemporaries.