Nanostring gene expression profiling for markers of Alzheimer's disease in MAPT P301S;cTFEB;HSACre and MAPT P301S male and female mice

To assess the potential neuroprotective effects of overexpressing skeletal muscle Transcription Factor EB (TFEB) signaling in the context of age-associated neurodegenerative disease pathologies, we derived cTFEB;HSACre transgenic mice in the MAPT P301S tau hyperphosphorylated background and used the Nanostring nCounter® Alzheimer’s Disease panel to gain more precise insights into disease-relevant transcriptional changes in the hippocampus in both male and female mice with both Tau hyperphosphorylation and skeletal muscle TFEB overexpression. We confirmed significantly reduced transcriptional activation of the nCounter AD microglial activation module through signature scoring. In this study, we utilized 6-month-old male and female MAPT301s;cTFEB;HSACre transgenic and MAPT P301S mouse hippocampi and the Nanostring nCounter® Alzheimer’s Disease panel which directly assesses the expression of 770 genes curated from human and pre-clinical models of AD and robustly captures disease-relevant signatures to examine the effects of overexpressing skeletal muscle TFEB signaling on a target brain region in a mouse model of tau pathology.