Whole Blood Transcriptome Characterization of 3xTg-AD Mouse and its modulation by transcranial Direct Current Stimulation (tDCS)

The 3xTg-AD mouse is a widely used model in the study of Alzheimer’s Disease (AD). It has been extensively characterized both from the anatomical and behavioral point of view but poorly studied at the transcriptomic level. For the first time, this study characterizes the whole blood transcriptome of the 3xTg-AD mouse at three and six months of age and evaluates how gene expression is modulated by transcranial direct current stimulation (tDCS). RNA-seq analysis revealed 183 differentially expressed genes (DEGs) that were a direct signature of the genetic background of the mouse. The expression profile of age-related genes in the 3 months-old 3xTg-AD mice was more similar to that of 6 months rather than 3 months-control mice, suggesting a premature aging of the 3xTg-AD mice. Moreover, in the 6 months-old 3xTg-AD mice, we observed a high number of DEGs that could represent good peripheral biomarkers of AD progression. Finally, tDCS was associated with gene expression changes in the 3xTg-AD but not in the control mice. In conclusion, this study provides a better molecular characterization of the 3xTg-AD mouse and suggests that blood gene expression can be used to identify new biomarkers of AD progression and treatments effect. Globally, the blood transcriptome of 42 mice was sequenced. We identified 6 sample groups stratified by mouse strain, age and treatment: three 3-months-old (3 mo.) 3xTg-AD mice; nine 6-months-old (6 mo.) 3xTg-AD mice; three 3 mo. C57BL/6 wild type (WT) mice; six 6 mo. C57BL/6 WT mice; fourteen 6 mo. 3xTg-AD mice underwent tDCS stimulation; seven 6 mo. C57BL/6 WT mice underwent tDCS stimulation