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

Abstract

Growing data suggest companion dogs may be a promising model of human brain aging and Alzheimer's disease (AD). However, although pathology is somewhat similar in canine cognitive dysfunction (CCD) and AD, the transcriptomic similarities between these two conditions have not been thoroughly evaluated. Two emerging transcriptome-related mechanisms of human 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 transcriptome (RNA-seq) data on prefrontal cortex tissue and plasma EVs from young, older, and older 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 CCD, including those related to novel RNA mechanisms of brain aging and AD, may be similar to those observed in humans.