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Updated: Jun 13, 2026
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DeepOmicsAE: Representing Signaling Modules in Alzheimer's Disease with Deep Learning Analysis of Proteomics, Metabolomics, and Clinical Data
Published on: December 15, 2023
Canonical Pathways Rewiring in Alzheimer's Disease.
Alejandro Pinta-Castro1,2, Gabriela Michel-Ureña1,2, Alejandra Paulina Pérez-González2,3
1Facultad Mexicana de Medicina, Universidad La Salle, México City 14100, Mexico.
International Journal of Molecular Sciences
|June 12, 2026
Summary
Alzheimer's disease involves disrupted gene networks, particularly in synaptic pathways. Our study reveals a rewiring process where key synaptic genes centralize, suggesting a structural reorganization in the brain.
Area of Science:
- Neuroscience
- Genomics
- Systems Biology
Background:
- Alzheimer's disease (AD) is a complex neurodegenerative disorder with poorly understood transcriptional disruptions.
- Existing research highlights multifactorial molecular pathway disruptions in AD.
Purpose of the Study:
- To investigate the structural mechanisms underlying transcriptional disintegration in Alzheimer's disease.
- To characterize gene co-expression network changes in the dorsolateral prefrontal cortex (DLPFC) in AD.
Main Methods:
- Constructed condition-specific gene co-expression networks using a mutual-information (MI) framework and infomap community partitioning on DLPFC bulk RNA-seq data.
- Performed functional enrichment analysis using Ingenuity Pathway Analysis (IPA).
- Integrated node degree with average expression and conducted shortest-path analysis to assess network topology and cohesion.
Main Results:
- Identified overrepresented pathways including GABAergic signaling, SNARE complex assembly, Synaptogenesis, and neurexin/neuroligin interactions.
- Observed topological centralization of key synaptic genes (e.g., NRXN2, SHANK1) alongside transcriptional downregulation in GABAergic and Synaptogenesis modules.
- Found consistent expansion of intra-pathway distances in AD, indicating reduced local co-expression cohesion.
Conclusions:
- Late-Onset Alzheimer's Disease (LOAD) is characterized by active structural rewiring of gene co-expression networks.
- The observed pattern suggests a consolidation of co-expression around synaptic components in AD.
- Cellular composition shifts may also contribute to observed signals in bulk RNA-seq data.
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