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Updated: May 13, 2026
04:41
Mapping Alzheimer's Disease Variants to Their Target Genes Using Computational Analysis of Chromatin Configuration
Published on: January 9, 2020
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Predictive gene expression signatures for Alzheimer's disease using post-mortem brain tissue.
Ashley H Duche1, Oliver Tan1, Andrius Baskys2
1Pharmacy Practice Department, School of Pharmacy, Chapman University, Irvine, CA, United States.
Frontiers in Aging Neuroscience
|October 20, 2025
Summary
This study identifies gene expression signatures that reveal molecular mechanisms of regional vulnerability in Alzheimer's Disease (AD). Findings highlight extracellular matrix processes and hormonal pathways, suggesting new therapeutic targets like FGFR inhibitors for AD.
Area of Science:
- Neuroscience
- Genomics
- Molecular Biology
Background:
- Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques and tau aggregates.
- Mechanisms of regional vulnerability in early AD pathogenesis are not fully understood.
- This study aimed to explore molecular mechanisms underlying regional susceptibility to AD pathology.
Purpose of the Study:
- To develop predictive gene expression signatures for regional vulnerability in Alzheimer's Disease.
- To identify molecular pathways and genetic factors contributing to differential AD pathology.
- To discover potential drug repurposing candidates for therapeutic intervention.
Main Methods:
- Utilized post-mortem brain tissues from ROSMAP, Mayo Clinic, and MSBB cohorts.
- Derived and validated gene expression signatures using Adaptive Signature Selection and InteGratioN (ASSIGN).
- Analyzed pathway dysregulation, genetic/sociodemographic factors, and identified drug candidates via CMAP.
Main Results:
- Predictive signatures distinguished AD activity and severity across six brain regions.
- Identified upregulation of extracellular matrix (ECM) processes and downregulation of hormonal signaling pathways.
- Found consistent upregulation of S100A4 and downregulation of CRH; highlighted influence of APOE genotype and sex; identified FGFR and bromodomain inhibitors as potential therapeutics.
Conclusions:
- Molecular signatures offer a framework for understanding AD progression drivers.
- ECM and hormonal pathways are key contributors to regional susceptibility in AD.
- Identified drug repurposing candidates warrant further investigation for AD treatment.
Keywords:
Alzheimer’s diseasedifferential gene expressiondifferentially expressed genesgene expression signaturespredictive gene signaturestranscriptomicsMore Related Videos
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