IGF2R circular RNA hsa_circ_0131235 expression in the middle temporal cortex is associated with AD pathology

Objective: To identify circular RNAs as candidates for differential expression in the middle temporal (MT) cortex in a well-characterized cohort with contrasting Alzheimer disease (AD) pathology and cognition. Top screen candidates were assessed for proof of circularity and then quantified by qPCR in a larger number of samples.

Methods: An initial RNA sequencing screen was performed on n = 20 frozen human tissue samples. Filters were applied to select candidate circular RNAs for further investigation. Frozen human tissue samples were selected for global AD pathology burden and global cognition scores (n = 100). Linear and divergent primers were used to assess circularity using RNaseR digestion. RT-qPCR was performed to quantify relative hsa_circ_0131235 abundance.

Results: Eleven circular RNAs were selected for further investigation. Four candidates produced circular RNA primers with appropriate efficiencies for qPCR. RNaseR treatment and analysis by both basic PCR and qPCR confirmed hsa_circ_0131235 circularity. There was a significant main effect of AD pathology on hsa_circ_0131235 expression.

Conclusions: Elevated hsa_circ_0131235 expression in the MT cortex was significantly associated with AD pathology.