Spatial Transcriptomics dataset of Alzheimer's disease mouse models (Tau22 and TauKO)
Gene expression is modulated by tau. We used two mouse models, THY-Tau22 mice, which express pro-aggregation tau, and TauKO mice, which are null for tau, to improve our understanding of tau-altered gene expression in brain. Spatial transcriptomics were used to interrogate regional expression changes. Focusing on the hippocampus and ventricles, two regions altered early in Alzheimer's disease, we identified the transthyretin gene, Ttr, as being dysregulated in a tau-dependent manner. Immunofluorescence (IF) revealed increased TTR protein expression in THY-Tau22 mice and lowered expression in TauKO mice in the choroid plexus epithelial cells. As TTR is involved in the clearance of Aß and the prevention of Aß aggregation, we evaluated endogenous mouse Aß in TauKO mice and observed increased Aß deposits. Our study reveals a hitherto unknown regulatory role of tau on Ttr gene and protein expression, which may participate to a feedback loop contributing to Aß disease progression.