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Lentivirus-mediated expression of human secreted amyloid precursor protein-alpha prevents development of memory and plasticity deficits in a mouse model of Alzheimer's disease

Overview of attention for article published in Molecular Brain, February 2018
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Title
Lentivirus-mediated expression of human secreted amyloid precursor protein-alpha prevents development of memory and plasticity deficits in a mouse model of Alzheimer's disease
Published in
Molecular Brain, February 2018
DOI 10.1186/s13041-018-0348-9
Pubmed ID
Authors

Valerie T. Y. Tan, Bruce G. Mockett, Shane M. Ohline, Karen D. Parfitt, Hollie E. Wicky, Katie Peppercorn, Lucia Schoderboeck, Mohamad Fairuz bin Yahaya, Warren P. Tate, Stephanie M. Hughes, Wickliffe C. Abraham

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease driven in large part by accumulated deposits in the brain of the amyloid precursor protein (APP) cleavage product amyloid-β peptide (Aβ). However, AD is also characterised by reductions in secreted amyloid precursor protein-alpha (sAPPα), an alternative cleavage product of APP. In contrast to the neurotoxicity of accumulated Αβ, sAPPα has many neuroprotective and neurotrophic properties. Increasing sAPPα levels has the potential to serve as a therapeutic treatment that mitigates the effects of Aβ and rescue cognitive function. Here we tested the hypothesis that lentivirus-mediated expression of a human sAPPα construct in a mouse model of AD (APPswe/PS1dE9), begun before the onset of plaque pathology, could prevent later behavioural and electrophysiological deficits. Male mice were given bilateral intra-hippocampal injections at 4 months of age and tested 8-10 months later. Transgenic mice expressing sAPPα performed significantly better than untreated littermates in all aspects of the spatial water maze task. Expression of sAPPα also resulted in partial rescue of long-term potentiation (LTP), tested in vitro. These improvements occurred in the absence of changes in amyloid pathology. Supporting these findings on LTP, lentiviral-mediated expression of sAPPα for 3 months from 10 months of age, or acute sAPPα treatment in hippocampal slices from 18 to 20 months old transgenic mice, completely reversed the deficits in LTP. Together these findings suggest that sAPPα has wide potential to act as either a preventative or restorative therapeutic treatment in AD by mitigating the effects of Aβ toxicity and enhancing cognitive reserve.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 69 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 69 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 13 19%
Student > Ph. D. Student 10 14%
Researcher 8 12%
Student > Master 8 12%
Student > Postgraduate 4 6%
Other 5 7%
Unknown 21 30%
Readers by discipline Count As %
Neuroscience 19 28%
Biochemistry, Genetics and Molecular Biology 8 12%
Agricultural and Biological Sciences 7 10%
Psychology 6 9%
Medicine and Dentistry 3 4%
Other 4 6%
Unknown 22 32%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 23 October 2018.
All research outputs
#14,973,306
of 23,031,582 outputs
Outputs from Molecular Brain
#634
of 1,123 outputs
Outputs of similar age
#257,615
of 442,601 outputs
Outputs of similar age from Molecular Brain
#15
of 20 outputs
Altmetric has tracked 23,031,582 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,123 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.0. This one is in the 39th percentile – i.e., 39% 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 442,601 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 20 others from the same source and published within six weeks on either side of this one. This one is in the 25th percentile – i.e., 25% of its contemporaries scored the same or lower than it.