Department of Neurology and Alzheimercenter Zuidwest Nederland, Erasmus Medical Center, Rotterdam, The Netherlands.
Department of Neurology and Alzheimercenter, Amsterdam Neuroscience, VU Medical Center, Amsterdam, The Netherlands.
Parkinsonism Relat Disord. 2017 Oct;43:1-8. doi: 10.1016/j.parkreldis.2017.07.009. Epub 2017 Jul 13.
The genetic architecture of dementia with Lewy bodies (DLB) is increasingly taking shape. Initially, genetic research focused mainly on linkage and candidate gene studies in small series of DLB patients. More recently, association and exome sequencing studies in larger groups have been conducted, and have shown that several variants in GBA and the APOE ε4 allele are important genetic risk factors for DLB. However, genetic research in DLB is still in its infancy. So far, many genetic studies have been biased and performed in clinically and pathologically heterogeneous populations. Therefore, it is likely that multiple DLB-specific genetic determinants still have to be identified. To further our understanding of the role of genetics in DLB, future genetic studies should be unbiased and performed in large series of DLB patients, ideally with both a clinical diagnosis and pathological confirmation. The combination of genomic techniques with other research modalities, such as proteomic research, is a promising approach to identify novel genetic determinants. More knowledge about the genetics of DLB will increase our understanding of the pathophysiology of the disease and its relation with Parkinson's Disease and Alzheimer's Disease, and may eventually lead to the development of disease modifying treatments.
路易体痴呆（DLB）的遗传结构越来越清晰。最初，遗传研究主要集中在小系列 DLB 患者的连锁和候选基因研究上。最近，更大群组的关联和外显子组测序研究已经进行，并表明 GBA 中的几个变体和 APOE ε4 等位基因是 DLB 的重要遗传风险因素。然而，DLB 的遗传研究仍处于起步阶段。到目前为止，许多遗传研究存在偏差，并且是在临床和病理异质人群中进行的。因此，很可能仍需要确定多个 DLB 特异性遗传决定因素。为了进一步了解遗传学在 DLB 中的作用，未来的遗传研究应该是无偏的，并在大量的 DLB 患者中进行，理想情况下是既有临床诊断又有病理证实。将基因组技术与其他研究模式（如蛋白质组学研究）相结合，是确定新的遗传决定因素的一种很有前途的方法。更多关于 DLB 遗传学的知识将增加我们对疾病病理生理学的理解及其与帕金森病和阿尔茨海默病的关系，并可能最终导致疾病修饰治疗的发展。
