- 學位論文
驗證血漿微型核糖核酸作為診斷巴金森氏病合併輕度認知功能障礙生物指標之研究
Validation of Plasma MicroRNA as the Diagnosis Biomarker in Parkinson’s disease with Mild Cognitive Impairment
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摘要
研究背景與目的 據觀察，巴金森氏病患者發生認知功能下降的風險，高於同年齡的健康對照組。由於診斷巴金森氏病合併輕度認知障礙具有困難度和複雜性，因此識別可信賴的生物指標是迫切的。作為潛在的生物指標之一，微型核糖核酸在與神經退化性疾病相關的各種病理機制中顯示出潛力。因此，本研究旨在探討血漿微型核糖核酸作為鑑別診斷巴金森氏病合併輕度認知障礙的生物指標。 研究方法 首先，我們先建立一個適合偵測微型核糖核酸的檢測平台。其次，再進行一項性別匹配的橫斷式研究，以決定由人類血漿中獲得的候選微型核糖核酸群。最後，使用微滴式數字聚合酶連鎖反應技術，我們驗證初始由小型核糖核酸定序分析，用於診斷巴金森氏病合併輕度認知障礙患者所選定的候選微型核糖核酸。 研究結果 結果顯示，miR-203a-3p/miR-16-5p 的比值在巴金森氏病合併輕度認知障礙患者的血漿中，與健康對照組相比顯著降低 (p = 0.02)。然而，miR-203a-3p/miR-16-5p 的比值在巴金森氏病合併輕度認知障礙的組別，與認知功能正常的巴金森氏病組別相比無統計顯著差異 (p = 0.27)。此外，KEGG 分析也顯示 miR-203a-3p 的目標基因群參與多種預測的生物路徑，包括甲狀腺激素信號路徑、多巴胺突觸路徑和膽鹼突觸路徑，而已知這些路徑對於老年人的認知障礙和神經退化疾病都有重大的影響。 結論 綜上所述，人類血漿中的 miR-203a-3p 可考慮作為檢測巴金森氏病患者合併認知功能退化的潛在生物指標。
並列摘要
Background and purpose The risk of developing cognitive decline had been observed to be higher in patients with Parkinson’s disease (PD) compared to the healthy controls at the matched age. Due to the difficulty and complexity of diagnosing Parkinson’s disease with mild cognitive impairment, it is urgent to identify reliable biomarkers. As one of the potential biological indicators, microRNA (miRNA) showed promise in various pathological mechanisms related to neurodegenerative disorders. Therefore, this study aimed to investigate the plasma miRNA as a diagnosis biomarker in Parkinson’s disease with mild cognitive impairment (PD-MCI). Method First, we established a suitable platform for miRNA detection. Second, a gender-matched and cross-sectional study was conducted to determine the miRNA candidates that were obtained from the human plasma. Finally, using droplet digital polymerase chain reaction technique (ddPCR), we validated the selected miRNA candidates that were initially profiled from small RNA sequencing in the diagnosis of patients with Parkinson’s disease associated with mild cognitive impairment. Result The results showed that the ratio of miR-203a-3p/miR-16-5p was significantly decreased in the plasma of Parkinson’s disease with mild cognitive impairment (PD-MCI) compared to healthy control (HC) (p = 0.02). However, no statistically significant difference was found in the ratio of miR-203a-3p/miR-16-5p between the groups of PDND and PD-MCI (p = 0.27). Moreover, KEGG analysis also revealed that the targeted genes of mir-203a-3p involve in the multiple predicted biological pathways, including thyroid hormone signaling pathway, cholinergic synapse and dopaminergic synapse, which were reported to make significant impact on the cognitive impairment in elders and neurodegenerative disorders. Conclusion In summary, miR-203a-3p in human plasma might serve as a potential biomarker for the detection of cognitive decline in patients with Parkinson’s disease.
參考文獻
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