Abstract：
Neurodegenerative diseases result from the interplay of abnormal gene expression and various pathological factors. Therefore, a disease-specific integrative genetic approach is required to understand the complexities and causes of target diseases. Recent studies have identified the correlation between genes encoding several transmembrane proteins, such as the cluster of differentiation (CD) and Alzheimer\'s disease (AD) pathogenesis. In this study, CD48 and CD40 gene expression in AD, a neurodegenerative disease, was analyzed to infer this link. Total RNA sequencing was performed using an Alzheimer\'s disease mouse model brain and blood, and gene expression was determined using a genome-wide association study (GWAS). We observed a marked elevation of CD48 and CD40 genes in Alzheimer\'s disease. Indeed, the upregulation of both CD48 and CD40 genes was significantly increased in the severe Alzheimer\'s disease group. With the elevation of CD48 and CD40 genes in Alzheimer\'s disease, associations of protein levels were also markedly increased in tissues. In addition, overexpression of CD48 and CD40 genes triggered tau aggregation, and co-expression of these genes accelerated aggregation. The nuclear factor kappa B (NF-ĸB) signaling pathway was enriched by CD48 and CD40 gene expression: it was also associated with tau pathology. Our data suggested that the CD48 and CD40 genes are novel AD-related genes, and this approach may be useful as a diagnostic or therapeutic target for the disease.
摘要：
神经退行性疾病是由异常基因表达和各种病理因素相互作用引起的。因此,需要一种疾病特异性的综合遗传方法来了解目标疾病的复杂性和原因。最近的研究已经确定了编码几种跨膜蛋白的基因之间的相关性，如分化集群(CD)和阿尔茨海默病(AD)的发病机制。在这项研究中,CD48和CD40基因在AD中的表达，一种神经退行性疾病,进行了分析以推断此链接。使用阿尔茨海默病小鼠模型脑和血液进行总RNA测序，并且使用全基因组关联研究(GWAS)确定基因表达。我们观察到阿尔茨海默病中CD48和CD40基因显著升高。的确,CD48和CD40基因的上调在重度阿尔茨海默病组中显著增加。随着CD48和CD40基因在阿尔茨海默病中的表达,组织中蛋白质水平的关联也显着增加。此外,CD48和CD40基因的过表达引发了tau聚集，这些基因的共表达加速了聚集。CD48和CD40基因表达富集了核因子κB（NF-κB）信号通路：它也与tau病理有关。我们的数据表明，CD48和CD40基因是新的AD相关基因，这种方法可以作为诊断或治疗该疾病的靶点。
