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Enduring Elevations of Hippocampal Amyloid Precursor Protein and Iron Are Features of β-Amyloid Toxicity and Are Mediated by Tau

Overview of attention for article published in Neurotherapeutics, October 2015
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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
Enduring Elevations of Hippocampal Amyloid Precursor Protein and Iron Are Features of β-Amyloid Toxicity and Are Mediated by Tau
Published in
Neurotherapeutics, October 2015
DOI 10.1007/s13311-015-0378-2
Pubmed ID
Authors

Xuling Li, Peng Lei, Qingzhang Tuo, Scott Ayton, Qiao-Xin Li, Steve Moon, Irene Volitakis, Rong Liu, Colin L Masters, David I Finkelstein, Ashley I Bush

Abstract

The amyloid cascade hypothesis of Alzheimer's disease (AD) positions tau protein as a downstream mediator of β-amyloid (Aβ) toxicity This is largely based on genetic cross breeding, which showed that tau ablation in young (3-7-month-old) transgenic mice overexpressing mutant amyloid precursor protein (APP) abolished the phenotype of the APP AD model. This evidence is complicated by the uncertain impact of overexpressing mutant APP, rather than Aβ alone, and for potential interactions between tau and overexpressed APP. Cortical iron elevation is also implicated in AD, and tau promotes iron export by trafficking APP to the neuronal surface. Here, we utilized an alternative model of Aβ toxicity by directly injecting Aβ oligomers into the hippocampus of young and old wild-type and tau knockout mice. We found that ablation of tau protected against Aβ-induced cognitive impairment, hippocampal neuron loss, and iron accumulation. Despite injected human Aβ being eliminated after 5 weeks, enduring changes, including increased APP levels, tau reduction, tau phosphorylation, and iron accumulation, were observed. While the results from our study support the amyloid cascade hypothesis, they also suggest that downstream effectors of Aβ, which propagate toxicity after Aβ has been cleared, may be tractable therapeutic targets.

X Demographics

X Demographics

The data shown below were collected from the profiles of 2 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 50 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 1 2%
Australia 1 2%
Unknown 48 96%

Demographic breakdown

Readers by professional status Count As %
Student > Master 8 16%
Student > Ph. D. Student 7 14%
Researcher 6 12%
Student > Bachelor 6 12%
Student > Doctoral Student 4 8%
Other 8 16%
Unknown 11 22%
Readers by discipline Count As %
Agricultural and Biological Sciences 7 14%
Neuroscience 6 12%
Biochemistry, Genetics and Molecular Biology 5 10%
Pharmacology, Toxicology and Pharmaceutical Science 4 8%
Psychology 4 8%
Other 10 20%
Unknown 14 28%
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 25 July 2016.
All research outputs
#3,621,629
of 25,373,627 outputs
Outputs from Neurotherapeutics
#377
of 1,308 outputs
Outputs of similar age
#47,090
of 286,873 outputs
Outputs of similar age from Neurotherapeutics
#12
of 19 outputs
Altmetric has tracked 25,373,627 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 1,308 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 18.2. This one has gotten more attention than average, scoring higher than 69% 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 286,873 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 36th percentile – i.e., 36% of its contemporaries scored the same or lower than it.