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Anti-α-synuclein immunotherapy reduces α-synuclein propagation in the axon and degeneration in a combined viral vector and transgenic model of synucleinopathy

Overview of attention for article published in Acta Neuropathologica Communications, January 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 (83rd percentile)
  • Average Attention Score compared to outputs of the same age and source

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Citations

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Title
Anti-α-synuclein immunotherapy reduces α-synuclein propagation in the axon and degeneration in a combined viral vector and transgenic model of synucleinopathy
Published in
Acta Neuropathologica Communications, January 2017
DOI 10.1186/s40478-016-0410-8
Pubmed ID
Authors

Brian Spencer, Elvira Valera, Edward Rockenstein, Cassia Overk, Michael Mante, Anthony Adame, Wagner Zago, Peter Seubert, Robin Barbour, Dale Schenk, Dora Games, Robert A. Rissman, Eliezer Masliah

Abstract

Neurodegenerative disorders such as Parkinson's Disease (PD), PD dementia (PDD) and Dementia with Lewy bodies (DLB) are characterized by progressive accumulation of α-synuclein (α-syn) in neurons. Recent studies have proposed that neuron-to-neuron propagation of α-syn plays a role in the pathogenesis of these disorders. We have previously shown that antibodies against the C-terminus of α-syn reduce the intra-neuronal accumulation of α-syn and related deficits in transgenic models of synucleinopathy, probably by abrogating the axonal transport and accumulation of α-syn in in vivo models. Here, we assessed the effect of passive immunization against α-syn in a new mouse model of axonal transport and accumulation of α-syn. For these purpose, non-transgenic, α-syn knock-out and mThy1-α-syn tg (line 61) mice received unilateral intra-cerebral injections with a lentiviral (LV)-α-syn vector construct followed by systemic administration of the monoclonal antibody 1H7 (recognizes amino acids 91-99) or control IgG for 3 months. Cerebral α-syn accumulation and axonopathy was assessed by immunohistochemistry and effects on behavior were assessed by Morris water maze. Unilateral LV-α-syn injection resulted in axonal propagation of α-syn in the contra-lateral site with subsequent behavioral deficits and axonal degeneration. Passive immunization with 1H7 antibody reduced the axonal accumulation of α-syn in the contra-lateral side and ameliorated the behavioral deficits. Together this study supports the notion that immunotherapy might improve the deficits in models of synucleinopathy by reducing the axonal propagation and accumulation of α-syn. This represents a potential new mode of action through which α-syn immunization might work.

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The data shown below were collected from the profile of 1 X user 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 109 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 109 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 21 19%
Student > Ph. D. Student 19 17%
Student > Master 12 11%
Student > Bachelor 12 11%
Student > Doctoral Student 6 6%
Other 14 13%
Unknown 25 23%
Readers by discipline Count As %
Neuroscience 22 20%
Biochemistry, Genetics and Molecular Biology 14 13%
Agricultural and Biological Sciences 14 13%
Medicine and Dentistry 9 8%
Immunology and Microbiology 5 5%
Other 17 16%
Unknown 28 26%
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 20 January 2017.
All research outputs
#3,218,247
of 22,940,083 outputs
Outputs from Acta Neuropathologica Communications
#703
of 1,387 outputs
Outputs of similar age
#68,288
of 421,590 outputs
Outputs of similar age from Acta Neuropathologica Communications
#13
of 19 outputs
Altmetric has tracked 22,940,083 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 1,387 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 421,590 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 83% of its contemporaries.
We're also able to compare this research output to 19 others from the same source and published within six weeks on either side of this one. This one is in the 31st percentile – i.e., 31% of its contemporaries scored the same or lower than it.