Plasma lncRNA signature of upregulated ATP2B1-AS1 and downregulated RPL21P28 correlates with diagnosis and cognitive severity in Alzheimer's disease

Abstract

Background: The non-invasive biomarkers have considerable effects in determination and treatment of Alzheimer's disease (AD). The specificity and stability of the circulating long non-coding RNAs (lncRNAs) have made them suitable options in disease management. The aim of this study was discovering and clinically confirming a new plasma lncRNA signature and the underlying regulatory mechanisms. Methods: In a two-stage research, the preliminary bioinformatic screen of public transcriptomic data (GEO: GSE63060) found candidate lncRNAs. Then the level of the major candidates, ATP2B1-AS1 and RPL21P28, were validated by Real-Time qPCR in plasma of 25 AD patients and 25 healthy controls. The diagnostic performance was appraised by the Receiver Operating Characteristic (ROC) curve analysis and the presumed functions were described by a competing endogenous RNA (ceRNA) network. Results: Our study established concurrent ATP2B1-AS1 upregulation and RPL21P28 downregulation in Alzheimer's patient plasma (p < 0.001). This highly discriminatory two-lncRNA signature produced an area under the curve (AUC) of 0.81 for ATP2B1-AS1 and 0.83 for RPL21P28. Based on MMSE scores, the expressions of both lncRNAs were significantly correlated with the level of cognitive impairment. These lncRNAs were also showed a correlation to important regulation mechanisms by our ceRNA network analysis, with RPL2B1P28 linked to synaptic functional genes and ATP2B1-AS1 to neurodevelopment. Conclusion: ATP2B1-AS1 and RPL21P28 plasma levels present specific AD biomarker signature. These lncRNAs show great potentials in designing a non-invasive blood test that can be used for early diagnosis and disease follow-up. It also establishes new areas for intervention therapy research.