Identification of circRNAs linked to Alzheimer’s disease and related dementias

ABSTRACT We conducted a circular-transcriptome-wide analysis and examined circRNA expression patterns associated with AD and clinical and neuropathological AD severity measures in human hippocampus and cortex brain regions. We validated prior studies of circRNA in AD cortex, and demonstrate novel patterns of expression in the AD hippocampus. We also examined circRNA expression across multiple types of dementia and show that circRNA expression differs by dementia subtype. We demonstrate robust circRNA expression in human neuronal precursor cells (NPCs). Then, using NPCs to study qPCR validated circRNA, we show that exposure to oligomeric tau elicits downregulation of circRNA similar to that observed in AD brain. These data identify circRNA that are changed with AD, and suggest that treating neuronal cells with oligomeric tau can recapitulate some of these changes.