EXPRESSION OF BLOOD EXOSOMAL miR-223 AND NUCLEOTIDE-BINDING OLIGOMERIZATION DOMAIN-LIKE RECEPTOR PROTEIN 3 IN PATIENTS WITH ALZHEIMER’S DISEASE AND THEIR CLINICAL SIGNIFICANCE

Abstract

Objective To investigate the expression levels of serum exosomal miR-223 and nucleotide-binding oligome-rization domain-like receptor protein 3 (NLRP3) in patients with Alzheimer’s disease (AD) and their association with the development and progression of AD. Methods A total of 65 elderly patients with AD who attended Department of Geriatrics in our hospital from March 2018 to December 2019 were enrolled as study group and were divided into mild cognitive impairment (MCI) subgroup with 41 patients and dementia of Alzheimer type (DAT) subgroup with 24 patients, and 60 elderly individuals with normal neurological function were enrolled as control group. Quantitative real-time PCR and ELISA were used to measure the expression levels of serum exosomal miR-223 and NLRP3. The Pearson and Spearman tests were used to analyze the correlation of serum exosomal miR-223 and NLRP3 with Mini-Mental State Examination (MMSE) score. The receiver operating characteristic (ROC) curve was plotted to calculate the area under the ROC curve (AUC) of serum exosomal miR-223 and NLRP3 in the diagnosis of MCI in AD patients or the differential diagnosis of DAT. Results Compared with the control group, the study group had a significantly lower expression level of serum exosomal miR-223 and a significantly higher expression level of NLRP3 (t=6.623,Z=-9.451,P<0.05), and compared with the MCI subgroup, the DAT subgroup had a significantly lower expression level of serum exosomal miR-223 and a significantly higher expression level of NLRP3 (t=3.190,Z=-5.288,P<0.05). In the study group, the expression level of serum exosomal miR-223 was negatively correlated with that of NLRP3 (r=-0.859,P<0.001) and was positively correlated with MMSE score (r=0.790,P<0.001), while the expression level of serum NLRP3 was negatively correlated with MMSE score (r=-0.776,P<0.001). Serum exosomal miR-223 combined with NLRP3 had an AUC of 0.91 (95%CI=0.86-0.97), a sensitivity of 89.0%, and a specificity of 76.5% in the diagnosis of MCI in AD patients, while it had an AUC of 0.81 (95%CI=0.75-0.88), a sensitivity of 70.0%, and a specifi-city of 85.0% in the differential diagnosis of DAT. Conclusion The miR-223/NLRP3 signaling pathway might be involved in the development and progression of AD, and measurement of serum exosomal miR-223 and NLRP3 has a certain value in the diagnosis of MCI or the differential diagnosis of DAT in AD patients, which requires further studies in the future.

Keywords

• alzheimer disease|cognitive dysfunction|micrornas|nlr family, pyrin domain-containing 3 protein|exosomes|area under curve|diagnosis|aged