Protein kinase CK2a' as a Dual Modulator of Immune Signaling and Synaptic Dysfunction in Tauopathy

Protein kinase CK2a' is upregulated in patients with tau-associated dementias and in the PS19 mouse model of tauopathy. CK2a' haploinsufficiency in the PS19 mouse model improved tau pathology, synaptic density, synaptic function, cognitive behavior and disease-associated microglia phenotypes. We hypothesized CK2a' haploinsufficiency would impact dysregulated gene expression in the PS19 model. We found that CK2a' haploinsufficiency led to enhanced synaptic gene network expression and enhance immune gene network expression. Overall design: RNA-Seq analysis of samples obtained from the hippocampus of ~7 month-old mice using: 4 Wildtype, 5 CK2a'(+/-), 3 high-pathology PS19, 4 low-pathology PS19 and 4 PS19;CK2a'(+/-) mice. Mice are on a mixed C57Bl/6 x B6C3H background. Animals were anesthetized with Avertin and intracardially perfused with Heparin in Tris-buffered Saline. Brains were dissected and hippocampus samples were flash frozen in liquid nitrogen prior to RNA extraction.