Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Prog Mol Biol Transl Sci. 2012;107:79-100. doi: 10.1016/B978-0-12-385883-2.00008-4.
Genetic factors play a major role in determining a person's risk to develop Alzheimer's disease (AD). Rare mutations transmitted in a Mendelian fashion within affected families, for example, APP, PSEN1, and PSEN2, cause AD. In the absence of mutations in these genes, disease risk is largely determined by common polymorphisms that, in concert with each other and nongenetic risk factors, modestly impact risk for AD (e.g., the ε4-allele in APOE). Recent genome-wide screening approaches have revealed several additional AD susceptibility loci and more are likely to be discovered over the coming years. In this chapter, we review the current state of AD genetics research with a particular focus on loci that now can be considered established disease genes. In addition to reviewing the potential pathogenic relevance of these genes, we provide an outlook into the future of AD genetics research based on recent advances in high-throughput sequencing technologies.
遗传因素在决定一个人患阿尔茨海默病（AD）的风险方面起着重要作用。例如，以孟德尔方式在受影响的家族中传递的罕见突变 APP、PSEN1 和 PSEN2 会导致 AD。在这些基因中没有突变的情况下，疾病风险主要由共同的多态性决定，这些多态性与其他非遗传风险因素一起，适度影响 AD 的风险（例如，APOE 中的 ε4-等位基因）。最近的全基因组筛查方法揭示了几个额外的 AD 易感性位点，在未来几年可能会发现更多的位点。在本章中，我们将特别关注现在可以被认为是确定的疾病基因的位点，回顾 AD 遗传学研究的现状。除了回顾这些基因的潜在致病相关性外，我们还基于高通量测序技术的最新进展，对 AD 遗传学研究的未来进行了展望。
