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Exosomes taken up by neurons hijack the endosomal pathway to spread to interconnected neurons

Overview of attention for article published in Acta Neuropathologica Communications, February 2018
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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 (82nd percentile)
  • Good Attention Score compared to outputs of the same age and source (66th percentile)

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Title
Exosomes taken up by neurons hijack the endosomal pathway to spread to interconnected neurons
Published in
Acta Neuropathologica Communications, February 2018
DOI 10.1186/s40478-018-0514-4
Pubmed ID
Authors

Juan Carlos Polanco, Chuanzhou Li, Nela Durisic, Robert Sullivan, Jürgen Götz

Abstract

In Alzheimer disease and related disorders, the microtubule-associated protein tau aggregates and forms cytoplasmic lesions that impair neuronal physiology at many levels. In addition to affecting the host neuron, tau aggregates also spread to neighboring, recipient cells where the misfolded tau aggregates, in a manner similar to prions, actively corrupt the proper folding of soluble tau, and thereby impair cellular functions. One vehicle for the transmission of tau aggregates are secretory nanovesicles known as exosomes. Here, we established a simple model of a neuronal circuit using a microfluidics culture system in which hippocampal neurons A and B were seeded into chambers 1 and 2, respectively, extending axons via microgrooves in both directions and thereby interconnecting. This system served to establish two models to track exosome spreading. In the first model, we labeled the exosomal membrane by coupling tetraspanin CD9 with either a green or red fluorescent tag. This allowed us to reveal that interconnected neurons exchange exosomes only when their axons extend in close proximity. In the second model, we added exosomes isolated from the brains of tau transgenic rTg4510 mice (i.e. exogenous, neuron A-derived) to neurons in chamber 1 (neuron B) interconnected with neuron C in chamber 2. This allowed us to demonstrate that a substantial fraction of the exogenous exosomes were internalized by neuron B and passed then on to neuron C. This transportation from neuron B to C was achieved by a mechanism that is consistent with the hijacking of secretory endosomes by the exogenous exosomes, as revealed by confocal, super-resolution and electron microscopy. Together, these findings suggest that fusion events involving the endogenous endosomal secretory machinery increase the pathogenic potential and the radius of action of pathogenic cargoes carried by exogenous exosomes.

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The data shown below were collected from the profiles of 12 X users 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 197 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 197 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 40 20%
Researcher 33 17%
Student > Master 21 11%
Student > Bachelor 21 11%
Student > Doctoral Student 9 5%
Other 22 11%
Unknown 51 26%
Readers by discipline Count As %
Neuroscience 43 22%
Biochemistry, Genetics and Molecular Biology 33 17%
Agricultural and Biological Sciences 25 13%
Engineering 9 5%
Medicine and Dentistry 8 4%
Other 26 13%
Unknown 53 27%
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 14 May 2021.
All research outputs
#3,273,065
of 23,023,224 outputs
Outputs from Acta Neuropathologica Communications
#742
of 1,394 outputs
Outputs of similar age
#85,145
of 474,288 outputs
Outputs of similar age from Acta Neuropathologica Communications
#8
of 24 outputs
Altmetric has tracked 23,023,224 research outputs across all sources so far. Compared to these this one has done well and is in the 85th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,394 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.8. This one is in the 46th percentile – i.e., 46% 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 474,288 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 82% of its contemporaries.
We're also able to compare this research output to 24 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 66% of its contemporaries.