China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Genes (Basel). 2023 Jan 30;14(2):353. doi: 10.3390/genes14020353.
Alzheimer's disease (AD) and ischemic stroke (IS) are common neurological disorders, and the comorbidity of these two brain diseases is often seen. Although AD and IS were regarded as two distinct disease entities, in terms of different etiologies and clinical presentation, recent genome-wide association studies (GWASs) revealed that there were common risk genes between AD and IS, indicating common molecular pathways and their common pathophysiology. In this review, we summarize AD and IS risk single nucleotide polymorphisms (SNPs) and their representative genes from the GWAS Catalog database, and find thirteen common risk genes, but no common risk SNPs. Furthermore, the common molecular pathways associated with these risk gene products are summarized from the GeneCards database and clustered into inflammation and immunity, G protein-coupled receptor, and signal transduction. At least seven of these thirteen genes can be regulated by 23 microRNAs identified from the TargetScan database. Taken together, the imbalance of these molecular pathways may give rise to these two common brain disorders. This review sheds light on the pathogenesis of comorbidity of AD and IS, and provides molecular targets for disease prevention, manipulation, and brain health maintenance.
阿尔茨海默病(AD)和缺血性中风(IS)是常见的神经退行性疾病,这两种脑部疾病常常同时存在。虽然 AD 和 IS 被认为是两种不同的疾病实体,具有不同的病因和临床表现,但最近的全基因组关联研究(GWAS)表明 AD 和 IS 之间存在共同的风险基因,提示存在共同的分子途径和共同的病理生理学。在这篇综述中,我们总结了来自 GWAS Catalog 数据库的 AD 和 IS 风险单核苷酸多态性(SNPs)及其代表性基因,发现了十三个共同的风险基因,但没有共同的风险 SNPs。此外,还从 GeneCards 数据库中总结了与这些风险基因产物相关的常见分子途径,并将其聚类为炎症和免疫、G 蛋白偶联受体和信号转导。至少有七个这样的基因可以被 TargetScan 数据库中鉴定的 23 个 microRNA 调控。综上所述,这些分子途径的失衡可能导致这两种常见的脑部疾病的发生。本综述揭示了 AD 和 IS 共病的发病机制,为疾病预防、干预和大脑健康维护提供了分子靶点。