Variations in the transcriptome of Alzheimer's disease reveal molecular networks involved in cardiovascular diseases
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Background: Because of its polygenic nature, Alzheimer's disease is believed to be caused not by defects in single genes, but rather by variations in a large number of genes and their complex interactions. A systems biology approach, such as the generation of a network of co-expressed genes and the identification of functional modules and cis-regulatory elements, to extract insights and knowledge from microarray data will lead to a better understanding of complex diseases such as Alzheimer's disease. In this study, we perform a series of analyses using co-expression networks, cis-regulatory elements, and functions of co-expressed gene modules to analyze single-cell gene expression data from normal and Alzheimer's disease-affected subjects. Results: We identified six co-expressed gene modules, each of which represented a biological process perturbed in Alzheimer's disease. Alzheimer's disease-related genes, such as APOE, A2M, PON2 and MAP4, and cardiovascular disease-associated genes, including COMT, CBS and WNK1, all congregated in a single module. Some of the disease-related genes were hub genes while many of them were directly connected to one or more hub genes. Further investigation of this disease-associated module revealed cis-regulatory elements that match to the binding sites of transcription factors involved in Alzheimer's disease and cardiovascular disease. Conclusion: Our results show the extensive links between Alzheimer's disease and cardiovascular disease at the co-expression and co-regulation levels, providing further evidence for the hypothesis that cardiovascular disease and Alzheimer's disease are linked. Our results support the notion that diseases in which the same set of biochemical pathways are affected may tend to co-occur with each other.
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Another study identified overlap in transcriptional networks between vascular disease and Alzheimer disease, suggesting potential molecular mechanisms underlying their co-occurrence.
“Another study used similar methods to identify overlap in transcriptional networks between vascular disease (a major risk factor for dementia) and Alzheimer disease, identifying potential molecular mechanisms that might underlie their co-occurrence151.”
From Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders (2015) · cites this paper as [151]
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- Authors
- Ray, M., Ruan, J., & Zhang, W.
- Affiliations
- Washington University in St. Louis (US)
- The University of Texas at San Antonio (US)
- Corresponding author
- Zhang, Weixiong
- Venue
- Genome Biology
- Published
- 2008-10-08
- Volume
- 9
- Issue
- 10
- Pages
- R148-R148
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- PMC
- PMC2760875
- OpenAlex
- W2125698969
- Cited by
- 119
- References
- 86
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 7 · 2023: 6 · 2022: 3 · 2021: 3 · 2020: 10 · 2019: 1 · 2018: 3 · 2017: 6 · 2016: 12 · 2015: 11 · 2014: 13 · 2013: 13 · 2012: 11
- FWCI
- 2.06
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, other-oa)
- Funders
- National Science Foundation (0535257, 0743797)
- Alzheimer's Association
- University of Texas at San Antonio
- University of California, Los Angeles
- National Heart, Lung, and Blood Institute (R01HL091028)
- 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, cardiovascular disease, transcriptome, co-expression network, gene modules, cis-regulatory elements, transcription factor binding sites, hub genes, apolipoprotein E, catechol-O-methyltransferase, WNK1, disease co-occurrence, single-cell gene expression
- MeSH terms
- Aged, 80 and over, Alzheimer Disease, Cardiovascular Diseases, Humans, Genetic Variation, Brain-Derived Neurotrophic Factor, Gene Expression Profiling, Systems Biology, Gene Regulatory Networks
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