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Unraveling the molecular mechanisms in severe Alzheimer's disease based on transcriptomic data using next generation
Hind A Alkhatabi1, Alaa G Alahmadi2, Muhammad Imran Naseer3
1Dr. Hind A. Alkhatabi, Ph.D. Department of Biological Science, College of Science, University of Jeddah, Jeddah, Saudi Arabia.
Pakistan Journal of Medical Sciences
|February 25, 2026
Summary
This study reveals key molecular pathways in severe Alzheimer's disease (AD), highlighting neuroinflammation and energy metabolism disruptions. Findings offer insights for improved AD diagnosis and therapies.
Area of Science:
- Neuroscience
- Genomics
- Molecular Biology
Background:
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline.
- Understanding the molecular underpinnings of severe AD is crucial for developing effective interventions.
Purpose of the Study:
- To decipher the molecular mechanisms of severe Alzheimer's disease (AD) using transcriptomic data.
- To identify key molecular pathways and gene networks implicated in the pathophysiology of severe AD.
Main Methods:
- Transcriptomic data from the dorsolateral prefrontal cortex (DLPFC) of severe AD patients and controls were analyzed.
- Next-generation knowledge discovery (NGKD) techniques, including GEO2R, WebGestalt, and Ingenuity Pathway Analysis (IPA), were employed.
- Differentially expressed genes (DEGs) were identified and subjected to pathway and network analyses.
Main Results:
- Over 3,000 differentially expressed genes (DEGs) were identified in the DLPFC of severe AD patients.
- Downregulated pathways included retrograde endocannabinoid signaling, oxidative phosphorylation, and ribosome biogenesis.
- Enriched pathways involved immune system activation, neuroinflammation, antigen processing, and presentation.
Conclusions:
- Severe AD is associated with dysregulated energy metabolism, impaired protein synthesis, and altered immunological responses.
- Neuroinflammation and mitochondrial damage are key molecular pathways implicated in AD progression.
- Findings contribute to understanding AD pathophysiology and developing diagnostic and therapeutic strategies.
Keywords:
Alzheimer’s diseaseDorsolateral prefrontal cortexGene set enrichment analysisIngenuity pathway analysisNeuroinflammationNext generation knowledge discoveryRNA sequencingWebGestaltrRNA processingMore Related Videos
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