Systematic Identification of circRNAs in Alzheimer’s Disease

Mammalian circRNAs are covalently closed circular RNAs often generated through backsplicing of precursor linear RNAs. Although their functions are largely unknown, they have been found to influence gene expression at different levels and in a wide range of biological processes. Here, we investigated if some circRNAs may be differentially abundant in Alzheimer’s Disease (AD). We identified and analyzed publicly available RNA-sequencing data from the frontal lobe, temporal cortex, hippocampus, and plasma samples reported from persons with AD and persons who were cognitively normal, focusing on circRNAs shared across these datasets. We identified an overlap of significantly changed circRNAs among AD individuals in the various brain datasets, including circRNAs originating from genes strongly linked to AD pathology such as DOCK1, NTRK2, APC (implicated in synaptic plasticity and neuronal survival) and DGL1/SAP97, TRAPPC9, and KIF1B (implicated in vesicular traffic). We further predicted the presence of circRNA isoforms in AD using specialized statistical analysis packages to create approximations of entire circRNAs. We propose that the catalog of differentially abundant circRNAs can guide future investigation on the expression and splicing of the host transcripts, as well as the possible roles of these circRNAs in AD pathogenesis.