Machine learning identifies candidates for drug repurposing in Alzheimer's disease

Nat Commun. 2021 Feb 15;12(1):1033. doi: 10.1038/s41467-021-21330-0.


Clinical trials of novel therapeutics for Alzheimer's Disease (AD) have consumed a large amount of time and resources with largely negative results. Repurposing drugs already approved by the Food and Drug Administration (FDA) for another indication is a more rapid and less expensive option. We present DRIAD (Drug Repurposing In AD), a machine learning framework that quantifies potential associations between the pathology of AD severity (the Braak stage) and molecular mechanisms as encoded in lists of gene names. DRIAD is applied to lists of genes arising from perturbations in differentiated human neural cell cultures by 80 FDA-approved and clinically tested drugs, producing a ranked list of possible repurposing candidates. Top-scoring drugs are inspected for common trends among their targets. We propose that the DRIAD method can be used to nominate drugs that, after additional validation and identification of relevant pharmacodynamic biomarker(s), could be readily evaluated in a clinical trial.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Drug Repositioning
  • Drugs, Investigational / chemistry
  • Drugs, Investigational / pharmacology*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • High-Throughput Screening Assays
  • Humans
  • Machine Learning*
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Nootropic Agents / chemistry
  • Nootropic Agents / pharmacology*
  • Pharmacogenetics / methods
  • Pharmacogenetics / statistics & numerical data
  • Polypharmacology
  • Prescription Drugs / chemistry
  • Prescription Drugs / pharmacology*
  • Primary Cell Culture
  • Severity of Illness Index


  • Drugs, Investigational
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Nootropic Agents
  • Prescription Drugs