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Characterization of tau prion seeding activity and strains from formaldehyde-fixed tissue

Overview of attention for article published in Acta Neuropathologica Communications, June 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 (84th percentile)
  • Good Attention Score compared to outputs of the same age and source (71st percentile)

Mentioned by

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1 news outlet
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5 tweeters

Citations

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65 Dimensions

Readers on

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96 Mendeley
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Title
Characterization of tau prion seeding activity and strains from formaldehyde-fixed tissue
Published in
Acta Neuropathologica Communications, June 2017
DOI 10.1186/s40478-017-0442-8
Pubmed ID
Authors

Sarah K. Kaufman, Talitha L. Thomas, Kelly Del Tredici, Heiko Braak, Marc I. Diamond

Abstract

Tauopathies such as Alzheimer's disease (AD) feature progressive intraneuronal deposition of aggregated tau protein. The cause is unknown, but in experimental systems trans-cellular propagation of tau pathology resembles prion pathogenesis. Tau aggregate inoculation into mice produces transmissible pathology, and tau forms distinct strains, i.e. conformers that faithfully replicate and create predictable patterns of pathology in vivo. The prion model predicts that tau seed formation will anticipate neurofibrillary tau pathology. To test this idea requires simultaneous assessment of seed titer and immunohistochemistry (IHC) of brain tissue, but it is unknown whether tau seed titer can be determined in formaldehyde-fixed tissue. We have previously created a cellular biosensor system that uses flow cytometry to quantify induced tau aggregation and thus determine seed titer. In unfixed tissue from PS19 tauopathy mice that express 1 N,4R tau (P301S), we have measured tau seeding activity that precedes the first observable histopathology by many months. Additionally, in fresh frozen tissue from human AD subjects at early to mid-neurofibrillary tangle stages (NFT I-IV), we have observed tau seeding activity in cortical regions predicted to lack neurofibrillary pathology. However, we could not directly compare the same regions by IHC and seeding activity in either case. We now describe a protocol to extract and measure tau seeding activity from small volumes (.04 mm(3)) of formaldehyde-fixed tissue immediately adjacent to that used for IHC. We validated this method with the PS19 transgenic mouse model, and easily observed seeding well before the development of phospho-tau pathology. We also accurately isolated two tau strains, DS9 and DS10, from fixed brain tissues in mice. Finally, we have observed robust seeding activity in fixed AD brain, but not controls. The successful coupling of classical IHC with seeding and strain detection should enable detailed study of banked brain tissue in AD and other tauopathies.

Twitter Demographics

The data shown below were collected from the profiles of 5 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 96 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 96 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 29 30%
Researcher 14 15%
Student > Bachelor 9 9%
Professor 7 7%
Student > Master 6 6%
Other 15 16%
Unknown 16 17%
Readers by discipline Count As %
Neuroscience 32 33%
Biochemistry, Genetics and Molecular Biology 16 17%
Agricultural and Biological Sciences 10 10%
Medicine and Dentistry 4 4%
Pharmacology, Toxicology and Pharmaceutical Science 2 2%
Other 9 9%
Unknown 23 24%

Attention Score in Context

This research output has an Altmetric Attention Score of 11. 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 12 June 2017.
All research outputs
#1,042,839
of 11,351,976 outputs
Outputs from Acta Neuropathologica Communications
#91
of 471 outputs
Outputs of similar age
#42,014
of 267,447 outputs
Outputs of similar age from Acta Neuropathologica Communications
#4
of 14 outputs
Altmetric has tracked 11,351,976 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 471 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.9. This one has done well, scoring higher than 80% 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 267,447 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 14 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 71% of its contemporaries.