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Alzheimer's Disease: Overview01:26

Alzheimer's Disease: Overview

Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
Alzheimer Disease l: Introduction01:29

Alzheimer Disease l: Introduction

Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
Alzheimer Disease ll: Pathophysiology01:23

Alzheimer Disease ll: Pathophysiology

Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...

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Related Experiment Video

Updated: May 13, 2026

Mapping Alzheimer's Disease Variants to Their Target Genes Using Computational Analysis of Chromatin Configuration
04:41

Mapping Alzheimer's Disease Variants to Their Target Genes Using Computational Analysis of Chromatin Configuration

Published on: January 9, 2020

19.3K

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
PubMed
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.

Keywords:
Alzheimer’s diseasedifferential gene expressiondifferentially expressed genesgene expression signaturespredictive gene signaturestranscriptomics

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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.