The microRNA-485-3p concentration in salivary exosome-enriched extracellular vesicles is related to amyloid β deposition in the brain of patients with Alzheimer’s disease

Alzheimer's disease (AD) is an irreversible neurodegenerative disease characterized by progressive long-term memory loss and cognitive dysfunction. Neuroimaging tests for abnormal amyloid-β (Aβ) deposition are considered the most reliable methods for the diagnosis of AD; however, the cost for such testing is very high and generally not covered by national insurance systems. Accordingly, it is only recommended for individuals exhibiting clinical symptoms of AD supported by clinical cognitive assessments. Recently, it was suggested that dysregulated microRNA-485-3p (miRNA-485-3p) in the brain and cerebrospinal fluid is closely related to pathogenesis of AD. However, a relationship between circulating miRNA-485-3p in salivary exosome-enriched extracellular vesicles (EE-EV) and Aβ deposition in the brain has not been observed.Using quantitative real-time polymerase chain reaction, we analyzed miRNA-485-3p concentration in salivary EE-EV. We used receiver operating characteristic (ROC) curve analysis to evaluate its predictive value for Aβ positron emission tomography (Aβ-PET) positivity in patients with AD.Our results showed that the miRNA-485-3p concentration in salivary EE-EV isolated from patients with AD was significantly increased compared with that in the healthy controls (p < 0.0001). In the analysis of all participants, the miRNA-485-3p concentration was significantly increased in Aβ-PET-positive participants compared to Aβ-PET-negative participants (p < 0.0001). Further analysis using only AD patients also showed that the miRNA-485-3p concentration was significantly increased in Aβ-PET-positive AD patients vs. Aβ-PET-negative AD patients (p = 0.0063). The ROC curve analysis for differentiating Aβ-PET-positive and negative participants showed that the area under the curve for miRNA-485-3p was 0.9217.These findings suggested that the miRNA-485-3p concentration in salivary EE-EV was closely related to Aβ deposition in the brain and had high diagnostic accuracy for predicting Aβ-PET positivity.