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May 17, 2026Current pharmacogenomics and personalized medicine (Online)/Current pharmacogenomics and personalized medicine0 citations

Therapeutic Potential of Drug Repurposing in Alzheimer’s Disease:Advancing Toward Disease Modification

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SSShahin SaifiMPManish PathakSKSokindra Kumar

Key Points

  • To explore the therapeutic potential of repurposing drugs for modifying Alzheimer's disease and highlight the significance of patient stratification.
  • Conducted a narrative review through October 2025 using PubMed, Scopus, and Web of Science.
  • Included original research papers, reviews, and Phase I-III clinical trials in English.
  • Ranked agents based on mechanistic justification, translational value, and clinical data.
  • Several repurposed agents show neuroprotective or early disease-modifying signals in trials.
  • Variations in APOE genotype and other factors may influence treatment response.
  • Clinical signal identification may improve with biomarker-guided patient selection.

Abstract

Introduction: Alzheimer's disease is characterized by a build-up of amyloid-β, tau hyperphosphorylation, neuroinflammation, synaptic dysfunction, and cognitive decline. Presently available treatments mostly alleviate symptoms with minimal impact on disease modification. To highlight the importance of phenotypic and pharmacogenomic stratification and investigate the therapeutic potential of repurposing medications in AD Methods: A narrative review was conducted through October 2025 using PubMed, Scopus, and Web of Science. Original research papers, reviews, and English-language Phase I–III clinical trials were all included. The agents were ranked according to their mechanistic justification, translational value, and current clinical data. Results: Repurposed agents include anti-inflammatory agents, metabolic modulators, immunomodulatory agents, neuropsychiatric agents, and autophagy-related derivatives. In preclinical and early clinical trials, several show neuroprotective or early diseasemodifying signals. On the other hand, the results of many trials are unclear or inconsistent. Variations in APOE genotype, metabolic state, vascular comorbidities, and sex differences may affect the response to treatment. Discussion: Repurposing drugs has several advantages, such as reduced development timelines, cheaper costs, and established safety records. However, restricted stratified trial designs, regulatory restrictions, and biological variability all impede translation. Clinical signal identification may be enhanced by biomarker-guided patient selection and early management, according to evidence. Conclusion: Repurposing drugs is a sensible and encouraging approach to developing treatments for AD. Efficacy must be verified by rigorous, meticulously designed, and stratified clinical trials prior to widespread clinical integration.

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Saifi et al. (2026) studied this question.

synapsesocial.com/papers/6a095c147880e6d24efe2155https://doi.org/10.2174/0118756921465241260430050234
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