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Lessons learned about [F-18]-AV-1451 off-target binding from an autopsy-confirmed Parkinson’s case

Overview of attention for article published in Acta Neuropathologica Communications, October 2017
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  • Above-average Attention Score compared to outputs of the same age (56th percentile)
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3 tweeters

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46 Dimensions

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Title
Lessons learned about [F-18]-AV-1451 off-target binding from an autopsy-confirmed Parkinson’s case
Published in
Acta Neuropathologica Communications, October 2017
DOI 10.1186/s40478-017-0482-0
Pubmed ID
Authors

Marta Marquié, Eline E. Verwer, Avery C. Meltzer, Sally Ji Who Kim, Cinthya Agüero, Jose Gonzalez, Sara J. Makaretz, Michael Siao Tick Chong, Prianca Ramanan, Ana C. Amaral, Marc D. Normandin, Charles R. Vanderburg, Stephen N. Gomperts, Keith A. Johnson, Matthew P. Frosch, Teresa Gómez-Isla

Abstract

[F-18]-AV-1451 is a novel positron emission tomography (PET) tracer with high affinity to neurofibrillary tau pathology in Alzheimer's disease (AD). PET studies have shown increased tracer retention in patients clinically diagnosed with dementia of AD type and mild cognitive impairment in regions that are known to contain tau lesions. In vivo uptake has also consistently been observed in midbrain, basal ganglia and choroid plexus in elderly individuals regardless of their clinical diagnosis, including clinically normal whose brains are not expected to harbor tau pathology in those areas. We and others have shown that [F-18]-AV-1451 exhibits off-target binding to neuromelanin, melanin and blood products on postmortem material; and this is important for the correct interpretation of PET images. In the present study, we further investigated [F-18]-AV-1451 off-target binding in the first autopsy-confirmed Parkinson's disease (PD) subject who underwent antemortem PET imaging. The PET scan showed elevated [F-18]-AV-1451 retention predominantly in inferior temporal cortex, basal ganglia, midbrain and choroid plexus. Neuropathologic examination confirmed the PD diagnosis. Phosphor screen and high resolution autoradiography failed to show detectable [F-18]-AV-1451 binding in multiple brain regions examined with the exception of neuromelanin-containing neurons in the substantia nigra, leptomeningeal melanocytes adjacent to ventricles and midbrain, and microhemorrhages in the occipital cortex (all reflecting off-target binding), in addition to incidental age-related neurofibrillary tangles in the entorhinal cortex. Additional legacy postmortem brain samples containing basal ganglia, choroid plexus, and parenchymal hemorrhages from 20 subjects with various neuropathologic diagnoses were also included in the autoradiography experiments to better understand what [F-18]-AV-1451 in vivo positivity in those regions means. No detectable [F-18]-AV-1451 autoradiographic binding was present in the basal ganglia of the PD case or any of the other subjects. Off-target binding in postmortem choroid plexus samples was only observed in subjects harboring leptomeningeal melanocytes within the choroidal stroma. Off-target binding to parenchymal hemorrhages was noticed in postmortem material from subjects with cerebral amyloid angiopathy. The imaging-postmortem correlation analysis in this PD case reinforces the notion that [F-18]-AV-1451 has strong affinity for neurofibrillary tau pathology but also exhibits off-target binding to neuromelanin, melanin and blood components. The robust off-target in vivo retention in basal ganglia and choroid plexus, in the absence of tau deposits, meningeal melanocytes or any other identifiable binding substrate by autoradiography in the PD case reported here, also suggests that the PET signal in those regions may be influenced, at least in part, by biological or technical factors that occur in vivo and are not captured by autoradiography.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 70 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 70 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 19 27%
Student > Master 11 16%
Student > Ph. D. Student 9 13%
Professor 4 6%
Other 3 4%
Other 10 14%
Unknown 14 20%
Readers by discipline Count As %
Medicine and Dentistry 18 26%
Neuroscience 14 20%
Psychology 4 6%
Engineering 3 4%
Biochemistry, Genetics and Molecular Biology 2 3%
Other 8 11%
Unknown 21 30%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 26 October 2017.
All research outputs
#6,509,482
of 12,056,897 outputs
Outputs from Acta Neuropathologica Communications
#296
of 522 outputs
Outputs of similar age
#119,716
of 284,226 outputs
Outputs of similar age from Acta Neuropathologica Communications
#20
of 44 outputs
Altmetric has tracked 12,056,897 research outputs across all sources so far. This one is in the 44th percentile – i.e., 44% of other outputs scored the same or lower than it.
So far Altmetric has tracked 522 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.7. This one is in the 40th percentile – i.e., 40% 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 284,226 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 56% of its contemporaries.
We're also able to compare this research output to 44 others from the same source and published within six weeks on either side of this one. This one is in the 47th percentile – i.e., 47% of its contemporaries scored the same or lower than it.