Integrated multi-omics analysis of Alzheimer’s disease shows molecular signatures associated with disease progression and potential therapeutic targets
Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by the formation of amyloid plaques implicated in neuronal death. Genetics, age, and sex are the risk factors attributed to AD. Though omics studies have helped to identify pathways associated with AD, an inte...
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| Format: | Article |
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Nature Portfolio
2023-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-30892-6 |
| _version_ | 1797864968567128064 |
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| author | Pradeep Kodam R. Sai Swaroop Sai Sanwid Pradhan Venketesh Sivaramakrishnan Ramakrishna Vadrevu |
| author_facet | Pradeep Kodam R. Sai Swaroop Sai Sanwid Pradhan Venketesh Sivaramakrishnan Ramakrishna Vadrevu |
| author_sort | Pradeep Kodam |
| collection | DOAJ |
| description | Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by the formation of amyloid plaques implicated in neuronal death. Genetics, age, and sex are the risk factors attributed to AD. Though omics studies have helped to identify pathways associated with AD, an integrated systems analysis with the available data could help to understand mechanisms, potential biomarkers, and therapeutic targets. Analysis of transcriptomic data sets from the GEO database, and proteomic and metabolomic data sets from literature was performed to identify deregulated pathways and commonality analysis identified overlapping pathways among the data sets. The deregulated pathways included those of neurotransmitter synapses, oxidative stress, inflammation, vitamins, complement, and coagulation pathways. Cell type analysis of GEO data sets showed microglia, endothelial, myeloid, and lymphoid cells are affected. Microglia are associated with inflammation and pruning of synapses with implications for memory and cognition. Analysis of the protein-cofactor network of B2, B6, and pantothenate shows metabolic pathways modulated by these vitamins which overlap with the deregulated pathways from the multi-omics analysis. Overall, the integrated analysis identified the molecular signature associated with AD. Treatment with anti-oxidants, B2, B6, and pantothenate in genetically susceptible individuals in the pre-symptomatic stage might help in better management of the disease. |
| first_indexed | 2024-04-09T23:00:26Z |
| format | Article |
| id | doaj.art-3525b71463ce42689afa027c4aea87b3 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T23:00:26Z |
| publishDate | 2023-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-3525b71463ce42689afa027c4aea87b32023-03-22T10:59:51ZengNature PortfolioScientific Reports2045-23222023-03-0113111610.1038/s41598-023-30892-6Integrated multi-omics analysis of Alzheimer’s disease shows molecular signatures associated with disease progression and potential therapeutic targetsPradeep Kodam0R. Sai Swaroop1Sai Sanwid Pradhan2Venketesh Sivaramakrishnan3Ramakrishna Vadrevu4Department of Biological Sciences, Birla Institute of Technology and Science PilaniDisease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher LearningDisease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher LearningDisease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher LearningDepartment of Biological Sciences, Birla Institute of Technology and Science PilaniAbstract Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by the formation of amyloid plaques implicated in neuronal death. Genetics, age, and sex are the risk factors attributed to AD. Though omics studies have helped to identify pathways associated with AD, an integrated systems analysis with the available data could help to understand mechanisms, potential biomarkers, and therapeutic targets. Analysis of transcriptomic data sets from the GEO database, and proteomic and metabolomic data sets from literature was performed to identify deregulated pathways and commonality analysis identified overlapping pathways among the data sets. The deregulated pathways included those of neurotransmitter synapses, oxidative stress, inflammation, vitamins, complement, and coagulation pathways. Cell type analysis of GEO data sets showed microglia, endothelial, myeloid, and lymphoid cells are affected. Microglia are associated with inflammation and pruning of synapses with implications for memory and cognition. Analysis of the protein-cofactor network of B2, B6, and pantothenate shows metabolic pathways modulated by these vitamins which overlap with the deregulated pathways from the multi-omics analysis. Overall, the integrated analysis identified the molecular signature associated with AD. Treatment with anti-oxidants, B2, B6, and pantothenate in genetically susceptible individuals in the pre-symptomatic stage might help in better management of the disease.https://doi.org/10.1038/s41598-023-30892-6 |
| spellingShingle | Pradeep Kodam R. Sai Swaroop Sai Sanwid Pradhan Venketesh Sivaramakrishnan Ramakrishna Vadrevu Integrated multi-omics analysis of Alzheimer’s disease shows molecular signatures associated with disease progression and potential therapeutic targets Scientific Reports |
| title | Integrated multi-omics analysis of Alzheimer’s disease shows molecular signatures associated with disease progression and potential therapeutic targets |
| title_full | Integrated multi-omics analysis of Alzheimer’s disease shows molecular signatures associated with disease progression and potential therapeutic targets |
| title_fullStr | Integrated multi-omics analysis of Alzheimer’s disease shows molecular signatures associated with disease progression and potential therapeutic targets |
| title_full_unstemmed | Integrated multi-omics analysis of Alzheimer’s disease shows molecular signatures associated with disease progression and potential therapeutic targets |
| title_short | Integrated multi-omics analysis of Alzheimer’s disease shows molecular signatures associated with disease progression and potential therapeutic targets |
| title_sort | integrated multi omics analysis of alzheimer s disease shows molecular signatures associated with disease progression and potential therapeutic targets |
| url | https://doi.org/10.1038/s41598-023-30892-6 |
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