VIB Center for Brain & Disease Research, Leuven, Belgium.
Laboratory for the Research of Neurodegenerative Diseases, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven (University of Leuven), Leuven, Belgium.
Science. 2020 Oct 2;370(6512):61-66. doi: 10.1126/science.abb8575.
To provide better prevention and treatment, we need to understand the environmental and genetic risks of Alzheimer's disease (AD). However, the definition of AD has been confounded with dementia in many studies. Thus, overinterpretation of genetic findings with regard to mechanisms and drug targets may explain, in part, controversies in the field. Here, we analyze the different forms of genetic risk of AD and how these can be used to model disease. We stress the importance of studying gene variants in the right cell types and in the right pathological context. The lack of mechanistic understanding of genetic variation has become the major bottleneck in the search for new drug targets for AD.
为了提供更好的预防和治疗方法，我们需要了解阿尔茨海默病（AD）的环境和遗传风险。然而，在许多研究中，AD 的定义与痴呆症相混淆。因此，对遗传发现的机制和药物靶点的过度解释可能在一定程度上解释了该领域的争议。在这里，我们分析了 AD 的不同形式的遗传风险，以及如何利用这些风险来模拟疾病。我们强调了在正确的细胞类型和正确的病理环境中研究基因变异的重要性。缺乏对遗传变异的机制理解已成为寻找 AD 新药物靶点的主要瓶颈。
