Whole Blood Transcriptome Characterization of 3xTg-AD Mouse and Its Modulation by Transcranial Direct Current Stimulation (tDCS)

Int J Mol Sci. 2021 Jul 16;22(14):7629. doi: 10.3390/ijms22147629.


The 3xTg-AD mouse is a widely used model in the study of Alzheimer's Disease (AD). It has been extensively characterized from both the anatomical and behavioral point of view, but poorly studied at the transcriptomic level. For the first time, we characterize the whole blood transcriptome of the 3xTg-AD mouse at three and six months of age and evaluate how its gene expression is modulated by transcranial direct current stimulation (tDCS). RNA-seq analysis revealed 183 differentially expressed genes (DEGs) that represent a direct signature of the genetic background of the mouse. Moreover, in the 6-month-old 3xTg-AD mice, we observed a high number of DEGs that could represent good peripheral biomarkers of AD symptomatology onset. Finally, tDCS was associated with gene expression changes in the 3xTg-AD, but not in the control mice. In conclusion, this study provides an in-depth molecular characterization of the 3xTg-AD mouse and suggests that blood gene expression can be used to identify new biomarkers of AD progression and treatment effects.

Keywords: 3xTg-AD mouse; Alzheimer’s disease; RNA-Seq; transcranial direct current stimulation.

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / therapy
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Blood Cells / drug effects
  • Blood Cells / metabolism
  • Disease Models, Animal
  • Gene Expression Profiling / methods
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Transcranial Direct Current Stimulation / adverse effects*
  • Transcriptome / genetics*
  • Whole Exome Sequencing / methods
  • tau Proteins / metabolism


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • tau Proteins