Myers A J, Goate A M
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Curr Opin Neurol. 2001 Aug;14(4):433-40. doi: 10.1097/00019052-200108000-00002.
Of late-onset Alzheimer's disease patients 50% do not carry an apolipoprotein E epsilon 4 allele, indicating that there must be other genetic or environmental risk factors for the disease. During the past few years, both genetic linkage and candidate gene studies have been undertaken in order to identify novel genetic risk factors for late-onset Alzheimer's disease. Previous genome screens implicated a region of chromosome 12 that contains the genes that encode both alpha(2)-macroglobulin and the low-density lipoprotein receptor-related protein. However, candidate gene studies have produced mixed results with respect to both of these genes. New linkage studies now provide strong evidence for Alzheimer's disease susceptibility loci on chromosomes 9 and 10. The locus on chromosome 10 very probably modifies risk for Alzheimer's disease by modulating beta-amyloid-42 levels.
在晚发性阿尔茨海默病患者中，50%不携带载脂蛋白Eε4等位基因，这表明该疾病必定存在其他遗传或环境风险因素。在过去几年中，人们开展了遗传连锁和候选基因研究，以确定晚发性阿尔茨海默病的新遗传风险因素。先前的全基因组筛查涉及12号染色体的一个区域，该区域包含编码α2-巨球蛋白和低密度脂蛋白受体相关蛋白的基因。然而，关于这两个基因的候选基因研究结果不一。新的连锁研究现在为9号和10号染色体上的阿尔茨海默病易感基因座提供了有力证据。10号染色体上的基因座很可能通过调节β-淀粉样蛋白42水平来改变阿尔茨海默病的风险。
