Vogrinc David, Goričar Katja, Dolžan Vita
Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Front Aging Neurosci. 2021 Mar 18;13:646901. doi: 10.3389/fnagi.2021.646901. eCollection 2021.
Alzheimer's disease (AD) is a complex neurodegenerative disease, affecting a significant part of the population. The majority of AD cases occur in the elderly with a typical age of onset of the disease above 65 years. AD presents a major burden for the healthcare system and since population is rapidly aging, the burden of the disease will increase in the future. However, no effective drug treatment for a full-blown disease has been developed to date. The genetic background of AD is extensively studied; numerous genome-wide association studies (GWAS) identified significant genes associated with increased risk of AD development. This review summarizes more than 100 risk loci. Many of them may serve as biomarkers of AD progression, even in the preclinical stage of the disease. Furthermore, we used GWAS data to identify key pathways of AD pathogenesis: cellular processes, metabolic processes, biological regulation, localization, transport, regulation of cellular processes, and neurological system processes. Gene clustering into molecular pathways can provide background for identification of novel molecular targets and may support the development of tailored and personalized treatment of AD.
阿尔茨海默病（AD）是一种复杂的神经退行性疾病，影响着相当一部分人群。大多数AD病例发生在老年人中，疾病的典型发病年龄在65岁以上。AD给医疗保健系统带来了重大负担，并且由于人口迅速老龄化，该疾病的负担在未来将会增加。然而，迄今为止尚未开发出针对全面发作疾病的有效药物治疗方法。AD的遗传背景已得到广泛研究；众多全基因组关联研究（GWAS）确定了与AD发病风险增加相关的重要基因。本综述总结了100多个风险位点。其中许多位点甚至在疾病的临床前阶段都可能作为AD进展的生物标志物。此外，我们利用GWAS数据确定了AD发病机制的关键途径：细胞过程、代谢过程、生物调节、定位、运输、细胞过程调节和神经系统过程。将基因聚类到分子途径中可为识别新的分子靶点提供背景，并可能支持AD的定制化和个性化治疗的发展。
