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Cited by 76Alzheimer's disease research and treatmentsBioinformatics and Genomic NetworksDementia and Cognitive Impairment Research

Integrative Analysis of Hippocampus Gene Expression Profiles Identifies Network Alterations in Aging and Alzheimer’s Disease

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Lanke, Vinay, Moolamalla, S. T. R., Roy, Dipanjan, Vinod, P. K.·2018·Frontiers in Aging Neuroscience
DOI 10.3389/fnagi.2018.00153PMC PMC5974201
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Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder contributing to rapid decline in cognitive function and ultimately dementia. Most cases of AD occur in elderly and later years. There is a growing need for understanding the relationship between aging and AD to identify shared and unique hallmarks associated with the disease in a region and cell-type specific manner. Although genomic studies on AD have been performed extensively, the molecular mechanism of disease progression is still not clear. The major objective of our study is to obtain a higher-order network-level understanding of aging and AD, and their relationship using the hippocampal gene expression profiles of young (20-50 years), aging (70-99 years), and AD (70-99 years). The hippocampus is vulnerable to damage at early stages of AD and altered neurogenesis in the hippocampus is linked to the onset of AD. We combined the weighted gene co-expression network and weighted protein-protein interaction network-level approaches to study the transition from young to aging to AD. The network analysis revealed the organization of co-expression network into functional modules that are cell-type specific in aging and AD. We found that modules associated with astrocytes, endothelial cells and microglial cells are upregulated and significantly correlate with both aging and AD. The modules associated with neurons, mitochondria and endoplasmic reticulum are downregulated and significantly correlate with AD than aging. The oligodendrocytes module does not show significant correlation with neither aging nor disease. Further, we identified aging- and AD-specific interactions/subnetworks by integrating the gene expression with a human protein-protein interaction network. We found dysregulation of genes encoding protein kinases (FYN, SYK, SRC, PKC, MAPK1, ephrin receptors) and transcription factors (FOS, STAT3, CEBPB, MYC, NFKβ, and EGR1) in AD. Further, we found genes that encode proteins with neuroprotective function (14-3-3 proteins, PIN1, ATXN1, BDNF, VEGFA) to be part of the downregulated AD subnetwork. Our study highlights that simultaneously analyzing aging and AD will help to understand the pre-clinical and clinical phase of AD and aid in developing the treatment strategies.

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Authors
Lanke, V., Moolamalla, S. T. R., Roy, D., & Vinod, P. K.
Affiliations
  • International Institute of Information Technology, Hyderabad (IN)
  • National Brain Research Centre (IN)
Corresponding author
Vinod, P. K.
ORCID
Vinod, P. K.
Venue
Frontiers in Aging Neuroscience
Publisher
Frontiers Media SA
Published
2018-05-23
Volume
10
Pages
153-153
ISSN
1663-4365 (ISSN-L)
DOI
10.3389/fnagi.2018.00153
PMC
PMC5974201
OpenAlex
W2803108236
Cited by
76
References
11
Citations by year
2026: 4 · 2025: 12 · 2024: 6 · 2023: 8 · 2022: 11 · 2021: 13 · 2020: 11 · 2019: 8 · 2018: 2
FWCI
5.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Aging Neuroscience (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)
Funders
Science and Engineering Research Board (ECR/2016/000488)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, aging, hippocampus, gene co-expression network, protein-protein interaction network, astrocytes, microglia, endothelial cells, protein kinases, transcription factors, brain-derived neurotrophic factor, VEGF-A, preclinical Alzheimer's disease

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