Integration of Transcriptional Signatures from Brain Tissue and Plasma Extracellular Vesicles of a Preclinical Tauopathy Mouse Model [brain ncRNA-Seq]

We present a multi-compartment transcriptomic atlas of 9.6-month-old PS19 tauopathy mice compared with wild-type (WT) controls (n=8/group), profiling cortical mRNA, cortical non-coding RNA (ncRNA), and plasma small extra-cellular vesicle (pEV) ncRNA. In the PS19 cortex, mRNA sequencing identified 917 dif-ferentially expressed genes (DEGs), with microglial deconvolution revealing a robust transition toward disease-associated microglia (DAM) gene signature and downregulation of genes involved in oxidative phosphorylation and cholesterol biosynthesis relative to WT.

Cortical ncRNA profiling identified 466 differentially expressed ncRNAs, primarily circular RNAs (circRNAs; n=331). In pEVs, 822 ncRNAs were differentially abundant, of which 657 circRNAs were identified in PS19 compared to WT mice. Cross-compartment integration demonstrated that pEV miRNA gene targets functionally mirrored genes involved in the brain’s inflammatory and metabolic failure.