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The release and trans-synaptic transmission of Tau via exosomes

Overview of attention for article published in Molecular Neurodegeneration, January 2017
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About this Attention Score

  • 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 (68th percentile)

Mentioned by

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1 news outlet
twitter
7 tweeters

Citations

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239 Dimensions

Readers on

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456 Mendeley
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Title
The release and trans-synaptic transmission of Tau via exosomes
Published in
Molecular Neurodegeneration, January 2017
DOI 10.1186/s13024-016-0143-y
Pubmed ID
Authors

Yipeng Wang, Varun Balaji, Senthilvelrajan Kaniyappan, Lars Krüger, Stephan Irsen, Katharina Tepper, RamReddy Chandupatla, Walter Maetzler, Anja Schneider, Eckhard Mandelkow, Eva-Maria Mandelkow

Abstract

Tau pathology in AD spreads in a hierarchical pattern, whereby it first appears in the entorhinal cortex, then spreads to the hippocampus and later to the surrounding areas. Based on this sequential appearance, AD can be classified into six stages ("Braak stages"). The mechanisms and agents underlying the progression of Tau pathology are a matter of debate. Emerging evidence indicates that the propagation of Tau pathology may be due to the transmission of Tau protein, but the underlying pathways and Tau species are not well understood. In this study we investigated the question of Tau spreading via small extracellular vesicles called exosomes. Exosomes from different sources were analyzed by biochemical methods and electron microscopy (EM) and cryo-EM. Microfluidic devices that allow the culture of cell populations in different compartments were used to investigate the spreading of Tau. We show that Tau protein is released by cultured primary neurons or by N2a cells overexpressing different Tau constructs via exosomes. Neuron-derived exosomal Tau is hypo-phosphorylated, compared with cytosolic Tau. Depolarization of neurons promotes release of Tau-containing exosomes, highlighting the importance of neuronal activity. Using microfluidic devices we show that exosomes mediate trans-neuronal transfer of Tau depending on synaptic connectivity. Tau spreading is achieved by direct transmission of exosomes between neurons. In organotypic hippocampal slices, Tau-containing exosomes in conditioned medium are taken up by neurons and microglia, not astrocytes. In N2a cells, Tau assemblies are released via exosomes. They can induce inclusions of other Tau molecules in N2a cells expressing mutant human Tau. We also studied exosomes from cerebrospinal fluid in AD and control subjects containing monomeric and oligomeric Tau. Split-luciferase complementation reveals that exosomes from CSF can promote Tau aggregation in cultured cells. Our study demonstrates that exosomes contribute to trans-synaptic Tau transmission, and thus offer new approches to control the spreading of pathology in AD and other tauopathies.

Twitter Demographics

The data shown below were collected from the profiles of 7 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 456 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 <1%
Spain 1 <1%
Netherlands 1 <1%
Belgium 1 <1%
Unknown 452 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 102 22%
Student > Bachelor 70 15%
Researcher 69 15%
Student > Master 54 12%
Student > Doctoral Student 34 7%
Other 72 16%
Unknown 55 12%
Readers by discipline Count As %
Neuroscience 126 28%
Biochemistry, Genetics and Molecular Biology 106 23%
Agricultural and Biological Sciences 75 16%
Medicine and Dentistry 30 7%
Chemistry 11 2%
Other 39 9%
Unknown 69 15%

Attention Score in Context

This research output has an Altmetric Attention Score of 12. 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 06 August 2019.
All research outputs
#1,566,851
of 15,606,530 outputs
Outputs from Molecular Neurodegeneration
#143
of 634 outputs
Outputs of similar age
#52,169
of 386,621 outputs
Outputs of similar age from Molecular Neurodegeneration
#20
of 63 outputs
Altmetric has tracked 15,606,530 research outputs across all sources so far. Compared to these this one has done well and is in the 89th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 634 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.7. This one has done well, scoring higher than 76% 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 386,621 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 63 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 68% of its contemporaries.