Key findings: Mark4 deletion suppresses MHC-II-associated microglial activation and mitochondrial gene signatures in PS19 mice.

Background: We previously showed that deletion of Mark4 attenuates tau pathology, neurodegeneration, and behavioral deficits in PS19 tauopathy model mice (Sultanakhmetov et al., 2024). However, the cell-type-specific effects of MARK4 loss remain unclear.

Methods: 

Single-cell RNA-seq analysis

Fixed cortical cells from four mice/genotype were analyzed using the 10x Genomics Chromium Flex platform. Data were processed with Cell Ranger and Seurat.

qPCR analysis of isolated microglia

CD11b-positive microglia were isolated by magnetic sorting and analyzed by qPCR.

Results:

Single-cell RNA-seq identifies reduced MHC-II-associated microglial activation after Mark4 deletion.

qPCR confirmed reduced Cd74 and H2-Eb1 expression after Mark4 deletion.

Mark4 deletion reduced mitochondrial gene signature scores in PS19 microglia.