Cao Thien Hoang Minh, Le Anh Phuc Hoang, Tran Tai Tien, Huynh Vy Kim, Pham Bao Hoai, Le Thao Mai, Nguyen Quang Lam, Tran Thang Cong, Tong Trang Mai, Than The Ha Ngoc, Nguyen Tran Tran To, Ha Huong Thi Thanh
School of Biomedical Engineering, International University, Ho Chi Minh City, Vietnam.
Vietnam National University, Ho Chi Minh City, Vietnam.
Front Mol Neurosci. 2023 Dec 21;16:1308610. doi: 10.3389/fnmol.2023.1308610. eCollection 2023.
Circulating cell-free RNA (cfRNA) is a potential hallmark for early diagnosis of Alzheimer's Disease (AD) as it construes the genetic expression level, giving insights into the pathological progress from the outset. Profiles of cfRNA in Caucasian AD patients have been investigated thoroughly, yet there was no report exploring cfRNAs in the ASEAN groups. This study examined the gap, expecting to support the development of point-of-care AD diagnosis.
cfRNA profiles were characterized from 20 Vietnamese plasma samples (10 probable AD and 10 age-matched controls). RNA reads were subjected to differential expression (DE) analysis. Weighted gene correlation network analysis (WGCNA) was performed to identify gene modules that were significantly co-expressed. These modules' expression profiles were then correlated with AD status to identify relevant modules. Genes with the highest intramodular connectivity (module membership) were selected as hub genes. Transcript counts of differentially expressed genes were correlated with key AD measures-MMSE and MTA scores-to identify potential biomarkers.
136 genes were identified as significant AD hallmarks ( < 0.05), with 52 downregulated and 84 upregulated in the AD cohort. 45.6% of these genes are highly expressed in the hippocampus, cerebellum, and cerebral cortex. Notably, all markers related to chronic inflammation were upregulated, and there was a significant shift in all apoptotic markers. Three co-expressed modules were found to be significantly correlated with Alzheimer's status ( < 0.05; > 0.5). Functional enrichment analysis on these modules reveals an association with focal adhesion, nucleocytoplasmic transport, and metal ion response leading to apoptosis, suggesting the potential participation of these pathways in AD pathology. 47 significant hub genes were found to be differentially expressed genes with the highest connectivity. Six significant hub genes () were found to be significantly correlated with MTA and MMSE scores. Other significant transcripts () were found to be involved in inflammation and neuronal death. Overall, we have identified candidate transcripts in plasma cf-RNA that are differentially expressed and are implicated in inflammation and apoptosis, which can jumpstart further investigations into applying cf-RNA as an AD biomarker in Vietnam and ASEAN countries.
循环游离RNA（cfRNA）是阿尔茨海默病（AD）早期诊断的潜在标志，因为它能反映基因表达水平，从一开始就深入了解病理进展。白种人AD患者的cfRNA谱已得到充分研究，但尚无关于东盟人群cfRNA的报道。本研究探讨了这一差距，期望为即时护理AD诊断的发展提供支持。
从20份越南血浆样本（10例可能的AD患者和10例年龄匹配的对照）中表征cfRNA谱。对RNA读数进行差异表达（DE）分析。进行加权基因共表达网络分析（WGCNA）以识别显著共表达的基因模块。然后将这些模块的表达谱与AD状态相关联，以识别相关模块。选择模块内连通性（模块成员）最高的基因作为枢纽基因。将差异表达基因的转录本计数与关键AD指标——简易精神状态检查表（MMSE）和颞叶内侧萎缩（MTA）评分——相关联，以识别潜在的生物标志物。
136个基因被确定为显著的AD标志（<0.05），在AD队列中有52个下调，84个上调。这些基因中有45.6%在海马体、小脑和大脑皮层中高表达。值得注意的是，所有与慢性炎症相关的标志物均上调，所有凋亡标志物均有显著变化。发现三个共表达模块与阿尔茨海默病状态显著相关（<0.05；>0.5）。对这些模块的功能富集分析揭示了与粘着斑、核质运输以及导致细胞凋亡的金属离子反应的关联，表明这些途径可能参与AD病理过程。发现47个显著的枢纽基因是连通性最高的差异表达基因。发现6个显著的枢纽基因（）与MTA和MMSE评分显著相关。发现其他显著的转录本（）与炎症和神经元死亡有关。总体而言，我们在血浆cf-RNA中鉴定出了差异表达且与炎症和细胞凋亡有关的候选转录本，这可以推动在越南和东盟国家将cf-RNA作为AD生物标志物的进一步研究。
