Identification of lncRNA in circulating exosomes as potential biomarkers for MCI among the elderly.

Background: The abnormal expression of lncRNA in elderly patients with mild cognitive impairment (MCI), and the ability of exosomes to stably carry non-coding RNAs provide a reliable physiological basis for exosomal lncRNA in plasma as a biomarker of MCI.

Methods: This case-control study enrolled 155 patients with MCI and 155 healthy controls from a community-based population aged≥60 years. The expression profiles of lncRNA and mRNA in plasma exosomes were analyzed and validated using high-throughput RNA sequencing and qRT-PCR. Pathway enrichment analysis were performed on differentially expressed transcripts to screen for target lncRNAs and genes. Multivariate logistic regression models were used to construct clinical predictive models. The receiver operating characteristic curve was used to analyze the predictive value, with an 184-sample external database validated.

Results: 132 lncRNAs and 459 mRNAs were significantly changed in plasma exosomes of MCI patients compared to healthy controls. LINC001380, ENST00000484033, and ENST00000531087 were screened as candidate exo-lncRNAs for predicting MCI. In logistic regression models, odds ratios and 95%CI for target exo-IncRNAs in MCI patients compared to healthy controls were 1.15(1.03-1.28) for LINC001380, 1.21(1.10-1.34) for ENST00000484033, and 1.23(1.08-1.40) for ENST00000531087, respectively. ROC curve analysis showed that the AUC of the combined predicted probability of target lncRNAs was 70.0 %(64.1 %-76.0 %). In the external database, the AUC for the target genes ATP2A2 and PSEN1 was 69.5 %(61.8 %-77.15 %).

Conclusion: This study provided evidence for the specific expression of plasma exosomal lncRNAs in MCI and its possible biological mechanism. The combined detection of the expression levels of lncRNA-LINC001380, lncRNA-ENST00000484033, and lncRNA-ENST00000531087 in plasma exosomes may provide early diagnosis and prevention of cognitive impairment.