Evidence of emerging transcriptome mediators of Alzheimer's disease in canine cognitive dysfunction

Growing data suggest companion dogs may be a promising model of human brain aging and Alzheimer's disease (AD). However, while pathology is similar in AD and canine cognitive dysfunction (CCD), the transcriptomic similarities between these two conditions have not been thoroughly evaluated. Two emerging transcriptome-related mechanisms of brain aging and AD involve transposable elements (TEs) and microRNAs (miRNAs), which have the potential to be carried systemically and between cells by extracellular vesicles (EVs). To determine if evidence of these AD-related transcriptomic events might be present in CCD, we generated total transcriptome (RNA-seq) data on cortex tissue and plasma EVs from young, old, and old CCD dogs. We show that: 1) global transcriptome changes with CCD indicate reduced neuronal health; 2) TE transcripts increase with CCD in both the brain and plasma EVs; 3) brain- and disease-relevant miRNAs are present in the same EVs, and some of these miRNAs correlate with indices of cognitive function/CCD. Collectively, our data suggest that transcriptomic changes in the dog, including those related to novel RNA mechanisms of brain aging and disease, are similar to those observed in humans. Overall design: RNA-seq of RNA isolated from prefrontal cortex and plasma extracellular vesicles (EVs) of young, old, and canine cognitive dysfunction companion dogs