Saunders A M
Box 2900, Department of Medicine (Neurology), Duke University Medical Center, Durham, NC 27710, USA.
Pharmacogenomics. 2001 Aug;2(3):239-49. doi: 10.1517/14622416.2.3.239.
Alzheimer's disease (AD) is the most common cause of dementia in the elderly population. Three genes have been identified that cause the less common early-onset, familial cases of the disease: the amyloid precursor (APP) protein gene on chromosome 21, the presenilin 1 (PSEN1) gene on chromosome 14 and the presenilin 2 (PSEN2) gene on chromosome 1. Mutations in these genes account for << 2% of the total number of AD cases. More than 50% of the cases are late-onset and related to the apolipoprotein E (APOE) gene on chromosome 19. The apolipoprotein E locus is a susceptibility gene, with polymorphisms affecting both risk and age-of-onset of the disease. Intense efforts are underway to identify additional susceptibility genes and promising regions on chromosomes 6, 9, 10 and 12 have been identified through whole genome scans. In addition, the genetic basis of several other non-AD inherited dementias has been unravelled. Discovery of the genetically relevant genes will aid in the elucidation of the pathogenesis of AD. The high-throughput tools of pharmacogenomics for gene-to-function-to-target studies can provide a quicker means of monitoring how mutations and polymorphisms affect model systems' adaptations to the altered genes, possibly identifying signal transduction or biochemical pathways. This relevant information can then be used for drug target selection and pharmacogenetics.
阿尔茨海默病（AD）是老年人群中痴呆最常见的病因。已确定有三个基因会导致该病较少见的早发性家族病例：21号染色体上的淀粉样前体蛋白（APP）基因、14号染色体上的早老素1（PSEN1）基因以及1号染色体上的早老素2（PSEN2）基因。这些基因中的突变在AD病例总数中所占比例不到2%。超过50%的病例为晚发性，且与19号染色体上的载脂蛋白E（APOE）基因有关。载脂蛋白E基因座是一个易感基因，其多态性会影响疾病的风险和发病年龄。目前正在大力努力寻找其他易感基因，通过全基因组扫描已在6号、9号、10号和12号染色体上确定了有前景的区域。此外，其他几种非AD遗传性痴呆的遗传基础也已被阐明。发现与遗传相关的基因将有助于阐明AD的发病机制。药物基因组学用于基因到功能再到靶点研究的高通量工具可以提供一种更快的方法来监测突变和多态性如何影响模型系统对基因改变的适应性，可能会识别信号转导或生化途径。然后，这些相关信息可用于药物靶点选择和药物遗传学研究。
