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Monoamine oxidase B inhibitor, selegiline, reduces 18F-THK5351 uptake in the human brain

Overview of attention for article published in Alzheimer's Research & Therapy, March 2017
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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 (86th percentile)
  • Good Attention Score compared to outputs of the same age and source (75th percentile)

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Title
Monoamine oxidase B inhibitor, selegiline, reduces 18F-THK5351 uptake in the human brain
Published in
Alzheimer's Research & Therapy, March 2017
DOI 10.1186/s13195-017-0253-y
Pubmed ID
Authors

Kok Pin Ng, Tharick A. Pascoal, Sulantha Mathotaarachchi, Joseph Therriault, Min Su Kang, Monica Shin, Marie-Christine Guiot, Qi Guo, Ryuichi Harada, Robert A. Comley, Gassan Massarweh, Jean-Paul Soucy, Nobuyuki Okamura, Serge Gauthier, Pedro Rosa-Neto

Abstract

(18)F-THK5351 is a quinoline-derived tau imaging agent with high affinity to paired helical filaments (PHF). However, high levels of (18)F-THK5351 retention in brain regions thought to contain negligible concentrations of PHF raise questions about the interpretation of the positron emission tomography (PET) signals, particularly given previously described interactions between quinolone derivatives and monoamine oxidase B (MAO-B). Here, we tested the effects of MAO-B inhibition on (18)F-THK5351 brain uptake using PET and autoradiography. Eight participants (five mild cognitive impairment, two Alzheimer's disease, and one progressive supranuclear palsy) had baseline (18)F-AZD4694 and (18)F-THK5351 scans in order to quantify brain amyloid and PHF load, respectively. A second (18)F-THK5351 scan was conducted 1 week later, 1 h after a 10-mg oral dose of selegiline. Three out of eight patients also had a third (18)F-THK5351 scan 9-28 days after the selegiline administration. The primary outcome measure was standardized uptake value (SUV), calculated using tissue radioactivity concentration from 50 to 70 min after (18)F-THK5351 injection, normalizing for body weight and injected radioactivity. The SUV ratio (SUVR) was determined using the cerebellar cortex as the reference region. (18)F-THK5351 competition autoradiography studies in postmortem tissue were conducted using 150 and 500 nM selegiline. At baseline, (18)F-THK5351 SUVs were highest in the basal ganglia (0.64 ± 0.11) and thalamus (0.62 ± 0.14). In the post-selegiline scans, the regional SUVs were reduced on average by 36.7% to 51.8%, with the greatest reduction noted in the thalamus (51.8%) and basal ganglia (51.4%). MAO-B inhibition also reduced (18)F-THK5351 SUVs in the cerebellar cortex (41.6%). The SUVs remained reduced in the three patients imaged at 9-28 days. Tissue autoradiography confirmed the effects of MAO-B inhibition on (18)F-THK5351 uptake. These results indicate that the interpretation of (18)F-THK5351 PET images, with respect to tau, is confounded by the high MAO-B availability across the entire brain. In addition, the heterogeneous MAO-B availability across the cortex may limit the interpretation of (18)F-THK5351 scans using reference region methods.

X Demographics

X Demographics

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 146 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 146 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 25 17%
Student > Ph. D. Student 23 16%
Student > Master 19 13%
Professor 10 7%
Student > Bachelor 10 7%
Other 21 14%
Unknown 38 26%
Readers by discipline Count As %
Neuroscience 34 23%
Medicine and Dentistry 33 23%
Chemistry 6 4%
Pharmacology, Toxicology and Pharmaceutical Science 6 4%
Psychology 6 4%
Other 19 13%
Unknown 42 29%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 16. 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 22 August 2023.
All research outputs
#2,300,821
of 25,402,889 outputs
Outputs from Alzheimer's Research & Therapy
#478
of 1,469 outputs
Outputs of similar age
#42,396
of 323,945 outputs
Outputs of similar age from Alzheimer's Research & Therapy
#8
of 28 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 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,469 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 67% 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 323,945 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 86% of its contemporaries.
We're also able to compare this research output to 28 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 75% of its contemporaries.