Circular RNA expression profile of Alzheimer’s disease and its clinical significance as biomarkers for the disease risk and progression

• Published in: The international journal of biochemistry & cell biology Vol. 123; p. 105747
• Main Authors: Li, Yuanlong, Fan, Hua, Sun, Jun, Ni, Ming, Zhang, Lei, Chen, Ci, Hong, Xuejiao, Fang, Fengqin, Zhang, Wei, Ma, Peizhi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.06.2020
• Subjects: Aged; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - genetics; Alzheimer’s disease; Amyloid beta-Peptides - cerebrospinal fluid; Amyloid beta-Peptides - genetics; Amyloid beta-Peptides - metabolism; biomarkers; Biomarkers - cerebrospinal fluid; cerebrospinal fluid; circular RNA; clinical significance; cytotoxicity; disease control; Disease Progression; Down-Regulation; expression profile; Female; Gene Ontology; Humans; Killer Cells, Natural - immunology; Logistic Models; Male; Microarray Analysis; microarray technology; MicroRNAs - cerebrospinal fluid; MicroRNAs - genetics; Middle Aged; mini-mental state examination score; natural killer cells; Nerve Growth Factors - cerebrospinal fluid; Nerve Growth Factors - genetics; Non-Neuronal Cholinergic System - genetics; Peptide Fragments - cerebrospinal fluid; Peptide Fragments - genetics; Peptide Fragments - metabolism; quantitative polymerase chain reaction; Real-Time Polymerase Chain Reaction; regression analysis; reverse transcription; reverse transcription quantitative polymerase chain reaction; risk; RNA, Circular - cerebrospinal fluid; RNA, Circular - genetics; ROC Curve; Signal Transduction - genetics; synapse; tau Proteins - cerebrospinal fluid; tau Proteins - genetics; tau Proteins - metabolism; Up-Regulation; miRNAs; AUC; SD; PNS; MMSE; circular RNA; SAMP8; CSF; KEGG; RT-qPCR; reverse transcription quantitative polymerase chain reaction; mini-mental state examination score; AD; Aβ42; Alzheimer’s disease; CI; ROC; GO; Ctrl; clinical significance; SAMR1; PCA; CircRNAs; FC; expression profile
• ISSN: 1357-2725; 1878-5875; 1878-5875
• DOI: 10.1016/j.biocel.2020.105747

To investigate circular RNA (circRNA) expression profile via microarray, and further assess the potential of candidate circRNAs as biomarkers in Alzheimer’s disease (AD). CircRNA expression profile in cerebrospinal fluid from 8 AD patients and 8 control (Ctrl) subjects was assessed by microarray. Subsequently, 10 candidate circRNAs from microarray were validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in cerebrospinal fluid from 80 AD patients and 40 Ctrl subjects. By microarray, 112 circRNAs were upregulated and 51 circRNAs were downregulated in AD patients compared with Ctrl subjects, and these circRNAs were enriched in AD related pathways such as neurotrophin signaling pathway, natural killer cell mediated cytotoxicity and cholinergic synapse. By RT-qPCR, circ-LPAR1, circ-AXL and circ-GPHN were increased, whereas circ-PCCA, circ-HAUS4, circ-KIF18B and circ-TTC39C were decreased in AD patients compared with Ctrl subjects, and these circRNAs were disclosed to predict AD risk by receiver operating characteristics curve analysis. Further forward-stepwise multivariate logistic regression revealed that circ-AXL, circ-GPHN, circ-ITPR3, circ-PCCA and cic-TTC39C were independent predictive factors for AD risk. Besides, in AD patients, circ-AXL and circ-GPHN negatively correlated, while circ-PCCA and circ-HAUS4 positively correlated with mini–mental state examination score; Circ-AXL negatively correlated, while circ-PCCA, circ-HAUS4 and circ-KIF18B positively correlated with Aβ42; Circ-AXL and circ-GPHN positively correlated, whereas circ-HAUS4 negatively correlated with t-tau; Circ-AXL positively correlated with p-tau. Our study provides an overview of circRNA expression profile in AD, and identifies that circ-AXL, circ-GPHN and circ-PCCA hold clinical implications for guiding disease management in AD patients.