Progress in molecular genetics of Alzheimer's disease
Progress in molecular genetics of Alzheimer's disease
复制标题
DOI：
10.1177/107385849600200106
复制
发表时间：
1996-01-01
期刊：
影响因子：
5.6
通讯作者：
Schellenberg, GD
中科院分区：
文献类型：
--
作者：
Hisama, FM;Schellenberg, GD
最近密集的工作已经强调了几种形式的阿尔茨海默病（AD）的遗传基础。21号染色体上的淀粉样前体蛋白基因突变可导致早发性常染色体显性AD或遗传性脑出血伴淀粉样变性。在14号染色体上，第二个基因与70 - 90%的早发性家族性AD（FAD）相关，于1995年通过定位克隆被鉴定出来。还有一些基因与21号染色体或14号染色体没有连锁关系;第三个基因座（在1号染色体上）最近在一组被称为伏尔加德国人的家族的受影响后代中被鉴定出来。在晚发性（年龄> 65岁）AD中，19号染色体上的载脂蛋白E基因等位基因ε 4已明确显示为AD发展的危险因素，并且似乎改变疾病的发病年龄。新出现的情况是，AD是一种遗传复杂的异质性疾病。确切地说，这些遗传因素如何相互作用，并与其他尚未确定的遗传和非遗传（环境）因素，以产生AD的临床和病理结果仍有待阐明。
Recent intensive work has highlighted the genetic basis of several forms of Alzheimer's disease (AD). Mutations in the amyloid precursor protein gene on chromosome 21 can cause either an early-onset autosomal dominant AD or hereditary cerebral hemorrhage with amyloidosis. On chromosome 14, a second gene associated with 70 to 90% of early-onset familiar AD (FAD) was identified by positional cloning in 1995, Still other kindreds show no linkage to either chromosome 21 or chromosome 14; the third locus (on chromosome 1) was recently identified in affected descendants of a group of families known as the Volga Germans. In late-onset (age > 65 years) AD, the apolipoprotein E gene allele epsilon 4 on chromosome 19 has clearly been shown to be a risk factor for the development of AD and appears to modify the age of onset of the disease. The emerging picture is that AD is a genetically complex, heterogeneous disorder. Precisely how these genetic factors interact with each other and with other yet-to-be-identified genetic and nongenetic (environmental) factors to produce the clinical and pathologic findings in AD remains to be elucidated.