BIORCHESTRA Co. Ltd., 17, Techno 4-ro, Yuseong-gu, Daejeon 34013, South Korea.
Borame Medical Center, 20, Boramae-ro 5-gil, Dongjak-gu, Seoul 07061, South Korea.
Clin Biochem. 2023 Aug;118:110603. doi: 10.1016/j.clinbiochem.2023.110603. Epub 2023 Jun 22.
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.
DESIGN & METHODS: 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.
阿尔茨海默病（AD）是一种不可逆的神经退行性疾病，其特征是进行性长期记忆丧失和认知功能障碍。神经影像学测试异常淀粉样蛋白-β（Aβ）沉积被认为是 AD 诊断最可靠的方法；然而，这种测试的成本非常高，通常不在国家保险系统的覆盖范围内。因此，只有在临床认知评估支持 AD 临床症状的情况下，才建议进行这种测试。最近，有研究表明，大脑和脑脊液中失调的 microRNA-485-3p（miRNA-485-3p）与 AD 的发病机制密切相关。然而，尚未观察到唾液外泌体富集细胞外囊泡（EE-EV）中的循环 miRNA-485-3p与大脑中 Aβ沉积之间的关系。
使用实时定量聚合酶链反应分析唾液 EE-EV 中的 miRNA-485-3p 浓度。我们使用接收者操作特征（ROC）曲线分析来评估其对 AD 患者 Aβ 正电子发射断层扫描（Aβ-PET）阳性的预测价值。
我们的结果表明，AD 患者唾液 EE-EV 中分离的 miRNA-485-3p 浓度明显高于健康对照组（p<0.0001）。在所有参与者的分析中，Aβ-PET 阳性参与者的 miRNA-485-3p 浓度明显高于 Aβ-PET 阴性参与者（p<0.0001）。仅使用 AD 患者进行的进一步分析也表明，Aβ-PET 阳性 AD 患者的 miRNA-485-3p 浓度明显高于 Aβ-PET 阴性 AD 患者（p=0.0063）。用于区分 Aβ-PET 阳性和阴性参与者的 ROC 曲线分析表明，miRNA-485-3p 的曲线下面积为 0.9217。
这些发现表明，唾液 EE-EV 中的 miRNA-485-3p 浓度与大脑中的 Aβ 沉积密切相关，对预测 Aβ-PET 阳性具有很高的诊断准确性。
