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Cognitive and emotional alterations in App knock-in mouse models of Aβ amyloidosis

Overview of attention for article published in BMC Neuroscience, July 2018
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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 (80th percentile)

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2 tweeters

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Title
Cognitive and emotional alterations in App knock-in mouse models of Aβ amyloidosis
Published in
BMC Neuroscience, July 2018
DOI 10.1186/s12868-018-0446-8
Pubmed ID
Authors

Yasufumi Sakakibara, Michiko Sekiya, Takashi Saito, Takaomi C. Saido, Koichi M. Iijima

Abstract

Alzheimer's disease (AD), the most common cause of dementia, is characterized by the progressive deposition of amyloid-β (Aβ) peptides and neurofibrillary tangles. Mouse models of Aβ amyloidosis generated by knock-in (KI) of a humanized Aβ sequence provide distinct advantages over traditional transgenic models that rely on overexpression of amyloid precursor protein (APP). In App-KI mice, three familial AD-associated mutations were introduced into the endogenous mouse App locus to recapitulate Aβ pathology observed in AD: the Swedish (NL) mutation, which elevates total Aβ production; the Beyreuther/Iberian (F) mutation, which increases the Aβ42/Aβ40 ratio; and the Arctic (G) mutation, which promotes Aβ aggregation. AppNL-G-F mice harbor all three mutations and develop progressive Aβ amyloidosis and neuroinflammatory response in broader brain areas, whereas AppNL mice carrying only the Swedish mutation exhibit no overt AD-related pathological changes. To identify behavioral alterations associated with Aβ pathology, we assessed emotional and cognitive domains of AppNL-G-F and AppNL mice at different time points, using the elevated plus maze, contextual fear conditioning, and Barnes maze tasks. Assessments of emotional domains revealed that, in comparison with wild-type (WT) C57BL/6J mice, AppNL-G-F/NL-G-F mice exhibited anxiolytic-like behavior that was detectable from 6 months of age. By contrast, AppNL/NL mice exhibited anxiogenic-like behavior from 15 months of age. In the contextual fear conditioning task, both AppNL/NL and AppNL-G-F/NL-G-F mice exhibited intact learning and memory up to 15-18 months of age, whereas AppNL-G-F/NL-G-F mice exhibited hyper-reactivity to painful stimuli. In the Barnes maze task, AppNL-G-F/NL-G-F mice exhibited a subtle decline in spatial learning ability at 8 months of age, but retained normal memory functions. AppNL/NL and AppNL-G-F/NL-G-F mice exhibit behavioral changes associated with non-cognitive, emotional domains before the onset of definitive cognitive deficits. Our observations consistently indicate that AppNL-G-F/NL-G-F mice represent a model for preclinical AD. These mice are useful for the study of AD prevention rather than treatment after neurodegeneration.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 75 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 75 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 18 24%
Researcher 14 19%
Student > Master 7 9%
Student > Bachelor 6 8%
Student > Doctoral Student 6 8%
Other 10 13%
Unknown 14 19%
Readers by discipline Count As %
Neuroscience 23 31%
Agricultural and Biological Sciences 10 13%
Psychology 6 8%
Pharmacology, Toxicology and Pharmaceutical Science 4 5%
Biochemistry, Genetics and Molecular Biology 4 5%
Other 11 15%
Unknown 17 23%

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 03 August 2018.
All research outputs
#1,671,580
of 13,801,769 outputs
Outputs from BMC Neuroscience
#91
of 1,050 outputs
Outputs of similar age
#53,023
of 271,843 outputs
Outputs of similar age from BMC Neuroscience
#1
of 1 outputs
Altmetric has tracked 13,801,769 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,050 research outputs from this source. They receive a mean Attention Score of 3.7. This one has done particularly well, scoring higher than 91% 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 271,843 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 80% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them