Assessing circular RNAs in Alzheimer's disease and frontotemporal lobar degeneration

A circular-transcriptome-wide study has recently linked differential expression of circular RNAs (circRNAs) in brain tissue with Alzheimer's disease (AD). We aimed at replicating the major findings in an independent series of sporadic and familial AD. We also included cases with frontotemporal lobar degeneration (FTLD), comprising brain specimens with TDP-43 aggregates (FTLD-TDP43) and samples that presented Tau accumulation (FTLD-Tau). Using a quantitative polymerase chain reaction approach, we evaluated 8 circRNAs that surpassed the significant threshold in the former meta-analysis (circHOMER1, circDOCK1, circFMN1, circKCNN2, circRTN4, circMAN2A1, circMAP7, and circPICALM). Average expression changes between patients with AD and controls followed the same directions as previously reported. We also confirmed an exacerbated alteration in circRNA expression in the familial AD group compared with the sporadic forms. Two circRNAs (circHOMER1 and circKCNN2) also showed significant expression alterations in the group of FTLD-Tau and FTLD-TDP43, respectively. Overall, these results reinforce the conception that expression of circRNAs is different in AD, and also suggest a wider involvement of this particular class of RNA in other neurodegenerative dementias.