Brouwers Nathalie, Sleegers Kristel, Van Broeckhoven Christine
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium.
Ann Med. 2008;40(8):562-83. doi: 10.1080/07853890802186905.
Alzheimer's disease (AD) is a complex disorder of the central nervous system (CNS). Molecular genetic research has provided a wealth of information regarding the genetic etiology of this devastating disease. Identification and functional characterization of autosomal dominant mutations in the amyloid precursor protein gene (APP) and the presenilin genes 1 and 2 (PSEN1 and PSEN2) have contributed substantially to our understanding of the biological mechanisms leading towards CNS neurodegeneration in AD. Nonetheless, a large part of the genetic etiology remains unresolved, especially that of more common, sporadic forms of AD. While substantial efforts were invested in the identification of genetic risk factors underlying sporadic AD, using carefully designed genetic association studies in large patient-control groups, the only firmly established risk factor remains the epsilon4 allele of the apolipoprotein E gene (APOE). Nevertheless, one can expect that with the current availability of high-throughput genotyping platforms and dense maps of single-nucleotide polymorphisms (SNPs), large-scale genetic studies will eventually generate additional knowledge about the genetic risk profile for AD. This review provides an overview of the current understanding in the field of AD genetics, covering both the rare monogenic forms as well as recent developments in the search for novel AD susceptibility genes.
阿尔茨海默病（AD）是一种中枢神经系统（CNS）的复杂疾病。分子遗传学研究已经提供了大量关于这种毁灭性疾病遗传病因的信息。淀粉样前体蛋白基因（APP）以及早老素基因1和2（PSEN1和PSEN2）中常染色体显性突变的鉴定和功能表征，极大地促进了我们对AD中导致CNS神经退行性变的生物学机制的理解。尽管如此，很大一部分遗传病因仍未得到解决，尤其是更常见的散发性AD的遗传病因。虽然人们投入了大量精力，通过在大型患者-对照组中进行精心设计的基因关联研究来确定散发性AD的遗传风险因素，但唯一明确确立的风险因素仍然是载脂蛋白E基因（APOE）的ε4等位基因。然而，可以预期，随着目前高通量基因分型平台和单核苷酸多态性（SNP）密集图谱的可得性，大规模基因研究最终将产生关于AD遗传风险概况的更多知识。本综述概述了AD遗传学领域的当前认识，涵盖了罕见的单基因形式以及寻找新的AD易感基因的最新进展。
