Linking the association between circRNAs and Alzheimer’s disease progression by multi-tissue circular RNA characterization

Abstract

Alzheimer’s disease (AD) has devastating consequences for patients during its slow, progressive course. It is important to understand the pathology of AD onset. Recently, circular RNAs (circRNAs) have been found to participate in many human diseases including cancers and neurodegenerative conditions. In this study, we mined the published dataset on the AMP-AD Knowledge Portal from the Mount Sinai Brain Bank (MSBB) to describe the circRNA profiles at different AD stages in brain samples from four brain regions: anterior prefrontal cortex, superior temporal lobe, parahippocampal gyrus and inferior frontal gyrus. In total, we found 147 circRNAs to be differentially expressed (DE) for different AD severity levels in the four regions. We also characterized the mRNA-circRNA co-expression network and annotated the potential function of circRNAs based on the co-expressed modules. Based on our results, we found that the most circRNA-regulated region in AD patients with severe symptoms was the parahippocampal gyrus. The strongest negatively AD severity-correlated module in the parahippocampal gyrus was enriched in cognitive disability and pathological-associated pathways such as synapse organization and regulation of membrane potential. Finally, a regression model based on the expression pattern of DE circRNAs in the module could help to distinguish the disease severity of patients, further supporting a role for circRNAs in AD pathology. In conclusion, our findings indicate that circRNAs in parahippocampal gyrus are possible biomarkers and regulators of AD as well as potential therapeutic targets.

Epigenetics: Recent Advances and Its Role in the Treatment of Alzheimer's Disease

“…Circ-AXL, circ-GPHN, and circ-PCCA differ significantly between AD patients and normal controls by studying the circRNA expression profile in cerebrospinal fluid, which may be potential biomarkers in AD (141). In addition, 147 circRNAs are differentially expressed in different AD brain regions, most of which are found in the parahippocampal gyrus, supporting that circRNAs in the parahippocampal gyrus may be biomarkers in AD (142).…”

Competing Endogenous RNA Networks as Biomarkers in Neurodegenerative Diseases

“…Similar to the last study, Lo et al [ 108 ] investigated the circRNA profiles at different AD stages in four brain regions and constructed a circRNA-mRNA co-expressed network in the parahippocampal gyrus. In this net two circRNAs (hsa_circ_0000994 and hsa_circ_0005232) are originated from SLC8A1 , a gene that codes for Na+/Ca2+ Exchange Protein 1 (NCX1) which could exert a neuroprotective role in AD [ 180 ].…”

CircRNAs: Emerging Bladder Cancer Biomarkers and Targets

“…CircRNAs have been demonstrated to serve as miRNA sponges, regulate alternative splicing or transcription, bind to RNA binding proteins, perform rolling translation, encode proteins, as well as derive pseudo genes (4,5,35). CircRNAs are involved in many pathological processes, such as diabetes and its complications, nervous system disease, cardiovascular diseases as well as various tumors (5,(36)(37)(38)(39)(40)(41)(42)(43)(44).…”