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Drug Development.

Marina Bykova1,2, Reina Tonegawa Kuji3, Ehud Karavani4

  • 1Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

Network medicine identified doxycycline as a potential treatment to prevent Alzheimer's disease (AD) in elderly and Traumatic Brain Injury (TBI) patients. This approach combined gene data and electronic health records to find repurposable drugs.

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Area of Science:

  • Computational biology and bioinformatics
  • Neuroscience and neurodegenerative diseases
  • Pharmacology and drug discovery

Background:

  • Traumatic Brain Injury (TBI) is a significant risk factor for Alzheimer's disease (AD), yet effective treatments remain limited.
  • Network-medicine techniques integrating gene set data and electronic health records (EHRs) show promise for identifying drug repurposing candidates.
  • This study focuses on preventing AD in elderly populations and individuals with a history of TBI.

Purpose of the Study:

  • To identify potential drug repurposing candidates for Alzheimer's disease (AD) prevention using a network-based approach.
  • To validate network-predicted drugs through analysis of large-scale real-world patient data.
  • To investigate the efficacy of identified drugs in reducing AD incidence in at-risk populations.

Main Methods:

  • A network-based algorithm assessed gene set connectedness in a protein-protein interactome (PPI) network using permutation tests.
  • The algorithm linked human interactome and drug-target networks to rank potential drug candidates.
  • Top candidates were evaluated using MarketScan® insurance claims data, focusing on patients over 70.

Main Results:

  • Network analysis generated ranked drug lists based on 69 TBI and 144 AD genes.
  • Doxycycline prescription was associated with a significantly lower risk of AD development (RR=0.92, p=0.002) compared to anti-infectives and antibiotics.
  • Potential mechanisms include modulation of microglial activity and blood-brain barrier integrity.

Conclusions:

  • Combining network-based predictions with real-world patient data effectively identifies repurposable drugs for AD prevention.
  • Doxycycline emerges as a promising candidate treatment for preventing Alzheimer's disease.
  • The study highlights the potential of network medicine in drug discovery for neurodegenerative diseases.