Genetic dissection of Alzheimer disease, a heterogeneous disorder.
Genetic dissection of Alzheimer disease, a heterogeneous disorder.
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阿尔茨海默病（一种异质性疾病）的基因剖析。
DOI：
10.1073/pnas.92.19.8552
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发表时间：
1995
影响因子：
11.1
通讯作者：
Schellenberg,GD
中科院分区：
文献类型：
--
作者：
Schellenberg,GD
阿尔茨海默病（AD）的遗传学是复杂的，尚未完全了解。淀粉样前体蛋白基因（APP）突变可导致早发性常染色体显性AD。体外研究表明，表达突变APP的细胞过度产生A β肽的致病形式，A β肽是AD淀粉样蛋白的主要成分。然而，APP基因突变是所有早发性家族性AD的5%或更少的原因。14号染色体上的一个基因座与其他早发性AD家族中的AD有关，并且在发病年龄和下降速度方面代表了该疾病的最严重形式。目前正在尝试通过定位克隆方法鉴定AD3基因。至少有一个额外的早发性AD基因座仍有待定位。在晚发性AD中，载脂蛋白E基因等位基因f14是AD的危险因素。该等位基因似乎是一种剂量依赖性的发病年龄调节剂。该基因的等位基因可能是保护性的。其他迟发性易感因素仍有待确定。
The genetics of Alzheimer disease (AD) are complex and not completely understood. Mutations in the amyloid precursor protein gene (APP) can cause early-onset autosomal dominant AD. In vitro studies indicate that cells expressing mutant APPs overproduce pathogenic forms of the A beta peptide, the major component of AD amyloid. However, mutations in the APP gene are responsible for 5% or less of all early-onset familial AD. A locus on chromosome 14 is responsible for AD in other early-onset AD families and represents the most severe form of the disease in terms of age of onset and rate of decline. Attempts to identify the AD3 gene by positional cloning methods are underway. At least one additional early-onset AD locus remains to be located. In late-onset AD, the apolipoprotein E gene allele epsilon 4 is a risk factor for AD. This allele appears to act as a dose-dependent age-of-onset modifier. The epsilon 2 allele of this gene may be protective. Other late-onset susceptibility factors remain to be identified.