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Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice

Overview of attention for article published in Journal of Neuroinflammation, July 2012
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Among the highest-scoring outputs from this source (#32 of 1,238)
  • High Attention Score compared to outputs of the same age (95th percentile)
  • High Attention Score compared to outputs of the same age and source (97th percentile)

Mentioned by

news
1 news outlet
blogs
1 blog
twitter
4 tweeters
peer_reviews
1 peer review site
f1000
1 research highlight platform

Citations

dimensions_citation
258 Dimensions

Readers on

mendeley
359 Mendeley
Title
Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice
Published in
Journal of Neuroinflammation, July 2012
DOI 10.1186/1742-2094-9-151
Pubmed ID
Authors

Dimitrije Krstic, Amrita Madhusudan, Jana Doehner, Prisca Vogel, Tina Notter, Claudine Imhof, Abigail Manalastas, Martina Hilfiker, Sandra Pfister, Cornelia Schwerdel, Carsten Riether, Urs Meyer, Irene Knuesel

Abstract

Alzheimer's disease (AD) is the most prevalent form of age-related dementia, and its effect on society increases exponentially as the population ages. Accumulating evidence suggests that neuroinflammation, mediated by the brain's innate immune system, contributes to AD neuropathology and exacerbates the course of the disease. However, there is no experimental evidence for a causal link between systemic inflammation or neuroinflammation and the onset of the disease. The viral mimic, polyriboinosinic-polyribocytidilic acid (PolyI:C) was used to stimulate the immune system of experimental animals. Wild-type (WT) and transgenic mice were exposed to this cytokine inducer prenatally (gestation day (GD)17) and/or in adulthood. Behavioral, immunological, immunohistochemical, and biochemical analyses of AD-associated neuropathologic changes were performed during aging. We found that a systemic immune challenge during late gestation predisposes WT mice to develop AD-like neuropathology during the course of aging. They display chronic elevation of inflammatory cytokines, an increase in the levels of hippocampal amyloid precursor protein (APP) and its proteolytic fragments, altered Tau phosphorylation, and mis-sorting to somatodendritic compartments, and significant impairments in working memory in old age. If this prenatal infection is followed by a second immune challenge in adulthood, the phenotype is strongly exacerbated, and mimics AD-like neuropathologic changes. These include deposition of APP and its proteolytic fragments, along with Tau aggregation, microglia activation and reactive gliosis. Whereas Aβ peptides were not significantly enriched in extracellular deposits of double immune-challenged WT mice at 15 months, they dramatically increased in age-matched immune-challenged transgenic AD mice, precisely around the inflammation-induced accumulations of APP and its proteolytic fragments, in striking similarity to the post-mortem findings in human patients with AD. Chronic inflammatory conditions induce age-associated development of an AD-like phenotype in WT mice, including the induction of APP accumulations, which represent a seed for deposition of aggregation-prone peptides. The PolyI:C mouse model therefore provides a unique tool to investigate the molecular mechanisms underlying the earliest pathophysiological changes preceding fibrillary Aβ plaque deposition and neurofibrillary tangle formations in a physiological context of aging. Based on the similarity between the changes in immune-challenged mice and the development of AD in humans, we suggest that systemic infections represent a major risk factor for the development of AD.

Twitter Demographics

The data shown below were collected from the profiles of 4 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 359 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 3 <1%
France 2 <1%
Netherlands 2 <1%
Switzerland 2 <1%
United Kingdom 1 <1%
Mexico 1 <1%
Greece 1 <1%
Germany 1 <1%
Unknown 346 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 71 20%
Researcher 65 18%
Student > Bachelor 57 16%
Student > Master 50 14%
Student > Doctoral Student 19 5%
Other 60 17%
Unknown 37 10%
Readers by discipline Count As %
Agricultural and Biological Sciences 109 30%
Neuroscience 90 25%
Medicine and Dentistry 38 11%
Biochemistry, Genetics and Molecular Biology 31 9%
Immunology and Microbiology 14 4%
Other 24 7%
Unknown 53 15%

Attention Score in Context

This research output has an Altmetric Attention Score of 23. 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 11 January 2017.
All research outputs
#486,426
of 9,724,852 outputs
Outputs from Journal of Neuroinflammation
#32
of 1,238 outputs
Outputs of similar age
#4,443
of 100,997 outputs
Outputs of similar age from Journal of Neuroinflammation
#1
of 48 outputs
Altmetric has tracked 9,724,852 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 94th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,238 research outputs from this source. They receive a mean Attention Score of 4.8. This one has done particularly well, scoring higher than 97% 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 100,997 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 95% of its contemporaries.
We're also able to compare this research output to 48 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 97% of its contemporaries.