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Chronic adiponectin deficiency leads to Alzheimer’s disease-like cognitive impairments and pathologies through AMPK inactivation and cerebral insulin resistance in aged mice

Overview of attention for article published in Molecular Neurodegeneration, November 2016
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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 (84th percentile)
  • Average Attention Score compared to outputs of the same age and source

Mentioned by

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1 news outlet
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2 tweeters

Citations

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72 Dimensions

Readers on

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102 Mendeley
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Title
Chronic adiponectin deficiency leads to Alzheimer’s disease-like cognitive impairments and pathologies through AMPK inactivation and cerebral insulin resistance in aged mice
Published in
Molecular Neurodegeneration, November 2016
DOI 10.1186/s13024-016-0136-x
Pubmed ID
Authors

Roy Chun-Laam Ng, On-Yin Cheng, Min Jian, Jason Shing-Cheong Kwan, Philip Wing-Lok Ho, Kenneth King-Yip Cheng, Patrick Ka Kit Yeung, Lena Lei Zhou, Ruby Lai-Chong Hoo, Sookja Kim Chung, Aimin Xu, Karen Siu-Ling. Lam, Koon Ho Chan

Abstract

Insulin resistance is the major pathogenesis underlying type 2 diabetes mellitus (T2DM) and these patients have doubled risk of Alzheimer's disease (AD). Increasing evidence suggests that insulin resistance plays an important role in AD pathogenesis, possibly due to abnormal GSK3β activation, causing intra- and extracellular amyloid-beta (Aβ) accumulation. Adiponectin (APN) is an adipokine with insulin-sensitizing and anti-inflammatory effects. Reduced circulatory APN level is associated with insulin resistance and T2DM. The role of APN in AD has not been elucidated. In this study, we aim to examine if adiponectin deficiency would lead to cerebral insulin resistance, cognitive decline and Alzheimer's-like pathology in mice. To study the role of adiponectin in cognitive functions, we employed adiponectin-knockout (APN-KO) mice and demonstrated chronic APN deficiency in their CNS. Behavioral tests were performed to study the cognitions of male APN-KO mice. Brains and tissue lysates were collected to study the pathophysiological and molecular changes in the brain of APN-KO mice. SH-SY5Y neuroblastoma cell line was used to study the molecular mechanism upon APN and insulin treatment. Aged APN-deficient mice displayed spatial memory and learning impairments, fear-conditioned memory deficit as well as anxiety. These mice also developed AD pathologies including increased cerebral Aβ42 level, Aβ deposition, hyperphosphorylated Tau proteins, microgliosis and astrogliosis with increased cerebral IL-1β and TNFα levels that associated with increased neuronal apoptosis and reduced synaptic proteins levels, suggesting APN deficiency may lead to neuronal and synaptic loss in the brain. AD pathologies-associated APN-KO mice displayed attenuated AMPK phosphorylation and impaired insulin signaling including decreased Akt induction and increased GSK3β activation in the hippocampus and frontal cortex. Aged APN-KO mice developed hippocampal insulin resistance with reduced pAkt induction upon intracerebral insulin injection. Consistently, APN treatment in SH-SY5Y cells with insulin resistance and overexpressing Aβ induce higher pAkt levels through AdipoR1 upon insulin treatment whereas the induction was blocked by compound C, indicating APN can enhance neuronal insulin sensitivity through AMPK activation. Our results indicated that chronic APN deficiency inactivated AMPK causing insulin desensitization and elicited AD-like pathogenesis in aged mice which also developed significant cognitive impairments and psychiatric symptoms.

Twitter Demographics

The data shown below were collected from the profiles of 2 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 102 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 102 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 24 24%
Researcher 17 17%
Student > Bachelor 16 16%
Student > Master 8 8%
Other 6 6%
Other 19 19%
Unknown 12 12%
Readers by discipline Count As %
Neuroscience 19 19%
Medicine and Dentistry 15 15%
Biochemistry, Genetics and Molecular Biology 14 14%
Agricultural and Biological Sciences 13 13%
Pharmacology, Toxicology and Pharmaceutical Science 6 6%
Other 14 14%
Unknown 21 21%

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 March 2018.
All research outputs
#1,415,435
of 12,680,099 outputs
Outputs from Molecular Neurodegeneration
#168
of 548 outputs
Outputs of similar age
#57,921
of 371,286 outputs
Outputs of similar age from Molecular Neurodegeneration
#11
of 20 outputs
Altmetric has tracked 12,680,099 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 548 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.1. This one has gotten more attention than average, scoring higher than 67% 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 371,286 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 84% of its contemporaries.
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 45th percentile – i.e., 45% of its contemporaries scored the same or lower than it.