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Updated: Jun 11, 2026
09:47
DeepOmicsAE: Representing Signaling Modules in Alzheimer's Disease with Deep Learning Analysis of Proteomics, Metabolomics, and Clinical Data
Published on: December 15, 2023
Integrated Multi-Tissue Transcriptomics Reveals Antagonistic Pleiotropy in Aging and Alzheimer's Disease.
Rana Salihoglu1, Şehnaz Can2, Thomas Dandekar1
1Department of Bioinformatics, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Computational and Structural Biotechnology Journal
|June 10, 2026
Summary
Healthy aging preserves metabolic and mitochondrial functions, promoting resilience against Alzheimer's disease (AD). Conversely, AD is linked to immune activation and suppressed metabolic pathways, indicating vulnerability. This study identifies key genes and regulators involved in these distinct molecular trajectories.
Area of Science:
- Neuroscience
- Genomics
- Aging Research
Background:
- Aging is the primary risk factor for Alzheimer's disease (AD).
- Individual differences in cognitive aging suggest molecular resilience and vulnerability factors.
- Previous studies focused on age prediction or specific pathway signatures.
Purpose of the Study:
- Investigate distinct molecular trajectories associated with healthy aging and AD.
- Utilize an antagonistic pleiotropy (AP) framework to identify genes with opposing age and disease expression patterns.
- Compare transcriptomic profiles from human fibroblasts and brain tissue.
Main Methods:
- Integrated transcriptomic analysis of human dermal fibroblasts (GSE113957) and multi-region brain profiles (GSE48350).
- Applied an antagonistic pleiotropy (AP) framework to prioritize genes with opposing age and disease associations.
- Performed pathway and transcription-factor inference analyses.
Main Results:
- Healthy aging correlated with preserved metabolic, mitochondrial, and lipid-homeostasis pathways.
- Alzheimer's disease (AD) showed suppressed metabolic programs and increased inflammatory/immune activity.
- Identified AP-Vulnerability genes (e.g., TAC1) induced in AD and AP-Resilience genes (e.g., PTH2) increased in healthy aging.
- Metabolic programs linked to resilience; immune activation linked to vulnerability.
- Transcription factors PPARG, NFE2L2, and TEAD4 inferred as resilience-associated regulators.
Conclusions:
- Distinct molecular trajectories differentiate healthy aging from Alzheimer's disease (AD).
- Metabolic and mitochondrial preservation are associated with resilience.
- Immune activation and suppressed metabolic pathways are linked to AD vulnerability.
- Identified key genes and regulators potentially mediating these processes.
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