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Elevated LRRK2 autophosphorylation in brain-derived and peripheral exosomes in LRRK2 mutation carriers

Overview of attention for article published in Acta Neuropathologica Communications, November 2017
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  • Good Attention Score compared to outputs of the same age (66th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (63rd percentile)

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Title
Elevated LRRK2 autophosphorylation in brain-derived and peripheral exosomes in LRRK2 mutation carriers
Published in
Acta Neuropathologica Communications, November 2017
DOI 10.1186/s40478-017-0492-y
Pubmed ID
Authors

Shijie Wang, Zhiyong Liu, Tao Ye, Omar S. Mabrouk, Tyler Maltbie, Jan Aasly, Andrew B. West

Abstract

Missense mutations in the leucine-rich repeat kinase 2 (LRRK2) gene can cause late-onset Parkinson disease (PD). LRRK2 mutations increase LRRK2 kinase activities that may increase levels of LRRK2 autophosphorylation at serine 1292 (pS1292) and neurotoxicity in model systems. pS1292-LRRK2 protein can be packaged into exosomes and measured in biobanked urine. Herein we provide evidence that pS1292-LRRK2 protein is robustly expressed in cerebral spinal fluid (CSF) exosomes. In a novel cohort of Norwegian subjects with and without the G2019S-LRRK2 mutation, with and without PD, we quantified levels of pS1292-LRRK2, total LRRK2, and other exosome proteins in urine from 132 subjects and in CSF from 82 subjects. CSF and urine were collected from the same morning clinic visit in 55 of the participants. We found that total LRRK2 protein concentration was similar in exosomes purified from either CSF or urine but the levels did not correlate. pS1292-LRRK2 levels were higher in urinary exosomes from male and female subjects with a LRRK2 mutation. Male LRRK2 mutation carriers without PD had intermediate pS1292-LRRK2 levels compared to male carriers with PD and controls. However, female LRRK2 mutation carriers without PD had the same pS1292-LRRK2 levels compared to female carriers with PD. pS1292-LRRK2 levels in CSF exosomes were near saturated in most subjects, ten-fold higher on average than pS1292-LRRK2 levels in urinary exosomes, irrespective of LRRK2 mutation status or PD diagnosis. These results provide insights into the effects of LRRK2 mutations in both the periphery and brain in a well-characterized clinical population and show that LRRK2 protein in brain exosomes may be much more active than in the periphery in most subjects.

X Demographics

X Demographics

The data shown below were collected from the profiles of 6 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 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 %
Researcher 21 22%
Student > Ph. D. Student 20 21%
Student > Bachelor 8 8%
Student > Doctoral Student 8 8%
Other 8 8%
Other 10 10%
Unknown 21 22%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 22 23%
Neuroscience 22 23%
Agricultural and Biological Sciences 10 10%
Medicine and Dentistry 7 7%
Immunology and Microbiology 2 2%
Other 6 6%
Unknown 27 28%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. 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 07 January 2019.
All research outputs
#7,338,030
of 23,310,485 outputs
Outputs from Acta Neuropathologica Communications
#953
of 1,411 outputs
Outputs of similar age
#143,660
of 439,484 outputs
Outputs of similar age from Acta Neuropathologica Communications
#12
of 30 outputs
Altmetric has tracked 23,310,485 research outputs across all sources so far. This one has received more attention than most of these and is in the 68th percentile.
So far Altmetric has tracked 1,411 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 32nd percentile – i.e., 32% 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 439,484 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 66% of its contemporaries.
We're also able to compare this research output to 30 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 63% of its contemporaries.