No Evidence to Suggest that the Use of Acetylcholinesterase Inhibitors Confounds the Results of Two Blood-Based Biomarker Studies in Alzheimer's Disease

J Alzheimers Dis. 2015;47(3):741-50. doi: 10.3233/JAD-150289.


Background: There is an urgent need to discover Alzheimer's disease (AD) biomarkers that are both easily measured and reliable. Research into blood-based biomarkers for AD using transcriptomics and proteomics has been an attractive and promising area of research. However, to date researchers have not looked into the possibility of AD medication being a confounding factor in these studies.

Objective: This study explored whether acetylcholinesterase inhibitors (AChEIs), the main class of AD medication, are a confounding factor in AD blood biomarker studies.

Methods: The most promising blood transcriptomic and proteomic biomarkers from two recent studies were analyzed to determine if they were differentially expressed between AD subjects on AChEIs and subjects that were not.

Results: None of the gene or protein biomarkers analyzed were found to be significantly altered between subjects in either group.

Conclusion: This study found no evidence that AChEIs are a confounding factor in these published AD blood biomarker studies. Further work is needed to confirm that this is also the case for other proposed biomarkers.

Keywords: Alzheimer’s disease; blood; cholinesterase inhibitors; gene expression; microarray; protein; proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / blood*
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Apolipoprotein E4 / genetics
  • Biomarkers / blood
  • Cholinesterase Inhibitors / adverse effects
  • Cholinesterase Inhibitors / therapeutic use*
  • Cognitive Dysfunction / blood
  • Cognitive Dysfunction / drug therapy
  • Cognitive Dysfunction / genetics
  • Cohort Studies
  • Female
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Humans
  • Male
  • Mental Status Schedule
  • Microarray Analysis
  • Nootropic Agents / adverse effects
  • Nootropic Agents / therapeutic use*
  • Proteomics
  • Reproducibility of Results


  • Apolipoprotein E4
  • Biomarkers
  • Cholinesterase Inhibitors
  • Nootropic Agents