Profile of -Derived CircRNA and MRNA Variants in the Entorhinal Cortex of Alzheimer's Disease Patients

Genetic variants in , a microglia-related gene, are well-known risk factors for Alzheimer's disease (AD). Here, we report that originates from circular RNAs (circRNAs), a novel class of non-coding RNAs characterized by a covalent and stable closed-loop structure. First, divergent primers were designed to amplify circRNAs by RT-PCR, which were further assessed by Sanger sequencing. Then, additional primer sets were used to confirm back-splicing junctions. In addition, HMC3 cells were used to assess the microglial expression of circTREM2s. Three candidate circTREM2s were identified in control and AD human entorhinal samples. One of the circRNAs, circTREM2_1, was consistently amplified by all divergent primer sets in control and AD entorhinal cortex samples as well as in HMC3 cells. In AD cases, a moderate negative correlation (r = -0.434) was found between the global average area of Aβ deposits in the entorhinal cortex and circTREM2_1 expression level. In addition, by bioinformatics tools, a total of 16 miRNAs were predicted to join with circTREM2s. Finally, mRNA corresponding to four isoforms was profiled by RT-qPCR. mRNA levels were found elevated in entorhinal samples of AD patients with low or intermediate ABC scores compared to controls. To sum up, a novel circRNA derived from the gene, circTREM2_1, has been identified in the human entorhinal cortex and mRNA expression has been detected to increase in AD compared to controls. Unraveling the molecular genetics of the gene may help to better know the innate immune response in AD.