INTRODUCTIONDespite the recognized importance of including ethnic diversity in Alzheimer's disease (AD) research, substantial knowledge gaps remain, particularly in Asian populations.METHODSRNA sequencing was performed on blood samples from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) to perform differential gene expression (DGE), gene co‐expression network, gene‐set enrichment, and machine learning analyses for amyloid beta (Aβ) deposition on positron emission tomography.RESULTSDGE analysis identified 265 dysregulated genes associated with Aβ deposition and replicated three AD‐associated genes in an independent Korean cohort. Network analysis identified two modules related to pathways including a natural killer (NK) cell–mediated immunity. Machine learning analysis showed the classification of Aβ positivity improved with the inclusion of gene expression data.DISCUSSIONOur results in a Korean population suggest Aβ deposition‐associated genes are enriched in NK cell–mediated immunity, providing a better understanding of AD molecular mechanisms and yielding potential diagnostic and therapeutic strategies.Highlights Dysregulated genes were associated with amyloid beta (Aβ) deposition on positron emission tomography in a Korean cohort. Dysregulated genes in Alzheimer's disease were replicated in an independent Korean cohort. Gene network modules were associated with Aβ deposition. Natural killer (NK) cell proportion in blood was associated with Aβ deposition. Dysregulated genes were related to a NK cell–mediated immunity.

中文翻译：

---

韩国队列中 Aβ 沉积在 PET 上的全基因组转录组分析


引言尽管在阿尔茨海默病 （AD） 研究中纳入种族多样性的重要性已得到认可，但仍然存在巨大的知识差距，尤其是在亚洲人群中。方法对韩国阿尔茨海默病早期诊断和预测脑衰老研究 （KBASE） 的血液样本进行 RNA 测序，以执行差异基因表达 （DGE） 、基因共表达网络、基因集富集和机器学习分析，用于正电子发射断层扫描上淀粉样蛋白 β （Aβ） 沉积。结果DGE 分析确定了 265 个与 Aβ 沉积相关的失调基因，并在一个独立的韩国队列中复制了 3 个 AD 相关基因。网络分析确定了两个与通路相关的模块，包括自然杀伤 （NK） 细胞介导的免疫。机器学习分析显示，纳入基因表达数据后，Aβ 阳性的分类有所改善。讨论韩国人群的结果表明，Aβ 沉积相关基因在 NK 细胞介导的免疫中富集，从而更好地了解 AD 分子机制并产生潜在的诊断和治疗策略。亮点 在韩国队列中，失调的基因与正电子发射断层扫描上的淀粉样蛋白 β （Aβ） 沉积有关。阿尔茨海默病中失调的基因在一个独立的韩国队列中被复制。基因网络模块与 Aβ 沉积相关。血液中的自然杀伤 （NK） 细胞比例与 Aβ 沉积相关。失调基因与 NK 细胞介导的免疫有关。