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Modulation of Aβ42 in vivo by γ-secretase modulator in primates and humans

Overview of attention for article published in Alzheimer's Research & Therapy, August 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 (84th percentile)

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Title
Modulation of Aβ42 in vivo by γ-secretase modulator in primates and humans
Published in
Alzheimer's Research & Therapy, August 2015
DOI 10.1186/s13195-015-0137-y
Pubmed ID
Authors

I-Fang Ling, Todd E. Golde, Douglas R. Galasko, Edward H. Koo

Abstract

Ibuprofen is one of the nonsteroidal anti-inflammatory drugs that have been shown to selectively lower pathogenic amyloid beta-peptide (Aβ)42 without impairing overall γ-secretase activity in vitro. This γ-secretase modulator (GSM) activity has been hypothesized to contribute to the reduction in risk of developing Alzheimer's disease in chronic users of nonsteroidal anti-inflammatory drugs. However, it is unclear whether ibuprofen, within therapeutic dosing range, demonstrates GSM activity in humans. In this study, we evaluated the effects of ibuprofen and a second-generation GSM, GSM-1, on Aβ levels in cerebrospinal fluid and plasma of young nonhuman primates and humans. Five to seven conscious cynomolgus monkeys (Macaca fascicularis) were nontreated or treated with 30 mg/kg GSM-1 or 50 or 100 mg/kg ibuprofen and the plasma and cerebrospinal fluid were sampled at -8, 0 (baseline or right before treatment), 2, 4, 6, 8, 12, and 24 h postdosing. In addition, sixteen healthy human subjects were randomly assigned to receive either placebo or 800 mg ibuprofen given by intravenous administration and plasma were collected at 0 (before drug infusion), 0.5, 1, 2, 4, 6, 8, 10, and 24 h after dosing. A single dose of GSM-1 (30 mg/kg) decreased the ratio of Aβ42 to Aβ40 to 60 % in plasma and the ratio of Aβ42 to total Aβ to 65 % in cerebrospinal fluid from baseline to postdosing in monkeys. However, no significant changes were detected following ibuprofen treatment at 100 mg/kg. Consistent with the results from nonhuman primates, ibuprofen did not alter plasma Aβ levels in human volunteers after a single 800 mg dose. GSM-1 exerted potent lowering of the ratio of Aβ42 to Aβ40 in nonhuman primates but the hypothesized GSM activity of ibuprofen could not be demonstrated in nonhuman primates and humans after acute dosing.

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

Geographical breakdown

Country Count As %
Unknown 30 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 6 20%
Student > Ph. D. Student 5 17%
Unspecified 4 13%
Researcher 4 13%
Student > Doctoral Student 2 7%
Other 4 13%
Unknown 5 17%
Readers by discipline Count As %
Neuroscience 6 20%
Unspecified 4 13%
Medicine and Dentistry 4 13%
Agricultural and Biological Sciences 4 13%
Pharmacology, Toxicology and Pharmaceutical Science 3 10%
Other 3 10%
Unknown 6 20%
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 05 May 2016.
All research outputs
#2,941,791
of 22,818,766 outputs
Outputs from Alzheimer's Research & Therapy
#721
of 1,221 outputs
Outputs of similar age
#39,502
of 264,147 outputs
Outputs of similar age from Alzheimer's Research & Therapy
#12
of 16 outputs
Altmetric has tracked 22,818,766 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 1,221 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 24.1. This one is in the 36th percentile – i.e., 36% 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 264,147 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 84% of its contemporaries.
We're also able to compare this research output to 16 others from the same source and published within six weeks on either side of this one. This one is in the 25th percentile – i.e., 25% of its contemporaries scored the same or lower than it.