Long noncoding RNA MALAT1 and its target microRNA-125b are potential biomarkers for Alzheimer's disease management via interactions with FOXQ1, PTGS2 and CDK5.

This study aimed to investigate the intercorrelation among long noncoding RNA MALAT1 (lnc-MALAT1), microRNA-125b (miR-125b), FOXQ1, PTGS2 and CDK5, as well as their correlations with disease risk, severity and progression of Alzheimer's disease (AD). In total, 120 AD patients, 120 Parkinson's disease (PD) patients and 120 controls were enrolled. Cerebrospinal fluid (CSF) samples were collected from 50 AD patients, 50 PD patients and 50 controls; plasma samples were obtained from all participants. Lnc-MALAT1, miR-125b, FOXQ1, PTGS2 and CDK5 were detected by RT-qPCR. CSF lnc-MALAT1/FOXQ1 and plasma lnc-MALAT1 were downregulated, while CSF miR-125b/PTGS2/CDK5 and plasma miR-125b/PTGS2 were upregulated in AD patients compared to PD patients and controls, which differentiated AD patients from PD patients and controls, as demonstrated by ROC curve analyses. In AD patients, CSF/plasma lnc-MALAT1 negatively correlated with miR-125b and PTGS2 but positively correlated with FOXQ1; CSF/plasma miR-125b negatively correlated with FOXQ1 but positively correlated with PTGS2/CDK5. In addition, CSF/plasma lnc-MALAT1 and FOXQ1 correlated with alleviated disease severity, while miR-125b, PTGS2 and CDK5 correlated with exacerbated disease severity, which were manifested by their correlations with MMSE score, Aβ42, t-tau and p-tau in AD patients. However, their correlations with MMSE score, Aβ42, t-tau and p-tau were weak in PD patients and controls. Notably, CSF but not plasma lnc-MALAT1 and miR-125b could predict the MMSE score decline at 1 year, 2 years and 3 years in AD patients. In conclusion, lnc-MALAT1 and its target miR-125b are potential biomarkers for AD management via their intercorrelation with FOXQ1, PTGS2 and CDK5.