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Concerted Perturbation Observed in a Hub Network in Alzheimer’s Disease

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Liang, Dapeng, Han, Guangchun, Feng, Xuemei, Sun, Jiya, Duan, Yong, Lei, Hongxing·2012·PLoS ONE
DOI 10.1371/journal.pone.0040498PMC PMC3398025
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Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease involving the alteration of gene expression at the whole genome level. Genome-wide transcriptional profiling of AD has been conducted by many groups on several relevant brain regions. However, identifying the most critical dys-regulated genes has been challenging. In this work, we addressed this issue by deriving critical genes from perturbed subnetworks. Using a recent microarray dataset on six brain regions, we applied a heaviest induced subgraph algorithm with a modular scoring function to reveal the significantly perturbed subnetwork in each brain region. These perturbed subnetworks were found to be significantly overlapped with each other. Furthermore, the hub genes from these perturbed subnetworks formed a connected hub network consisting of 136 genes. Comparison between AD and several related diseases demonstrated that the hub network was robustly and specifically perturbed in AD. In addition, strong correlation between the expression level of these hub genes and indicators of AD severity suggested that this hub network can partially reflect AD progression. More importantly, this hub network reflected the adaptation of neurons to the AD-specific microenvironment through a variety of adjustments, including reduction of neuronal and synaptic activities and alteration of survival signaling. Therefore, it is potentially useful for the development of biomarkers and network medicine for AD.

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  • PXN was up-regulated in the hippocampus, superior frontal gyrus and post-central gyrus of AD brains, co-localizing with Aβ-containing plaques.

    “PXN was up-regulated in the hippocampus, superior frontal gyrus and post-central gyrus of AD brains, co-localizing with Aβ-containing plaques [66].”

    From Sex specific molecular networks and key drivers of Alzheimer’s disease (2023) · cites this paper as [66]

    The Discussion section ‘The Interplay between Aging and AD’ reports PXN up-regulation in SFG, HIP and PCG, but identifies this as a finding during aging, not specifically in AD brains. The Results section ‘Biological Relevance of the Hub Network’ reports PXN as a constituent of plaques based on a literature survey; it does not establish that PXN co-localizes with Aβ-containing plaques in those three regions. Page numbers are unavailable in our copy. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Liang, D., Han, G., Feng, X., Sun, J., Duan, Y., & Lei, H.
Affiliations
  • Chinese Academy of Sciences (CN)
  • University of California, Davis (US)
Corresponding author
  • Duan, Yong
  • Lei, Hongxing
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2012-07-16
Volume
7
Issue
7
Pages
e40498
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0040498
PMC
PMC3398025
OpenAlex
W2023148493
Cited by
93
References
9
Citations by year
2025: 1 · 2024: 18 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 6 · 2019: 3 · 2018: 6 · 2017: 12 · 2016: 8 · 2015: 12 · 2014: 8 · 2013: 10 · 2012: 1
FWCI
3.99
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • National Natural Science Foundation of China (30870474)
  • National Institutes of Health (GM79383)
  • National Institute of General Medical Sciences (GM79383, GM-67168, R01GM079383, R01GM067168)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, gene expression networks, hub genes, brain regions, disease progression biomarkers, network medicine, neural adaptation, synaptic activity, survival signaling
MeSH terms
Aging, Alzheimer Disease, Brain, Humans, Male, Nerve Net, Biomarkers, Neurofibrillary Tangles, Disease Progression, Genetic Predisposition to Disease, Drug Discovery, Plaque, Amyloid, Transcriptome

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