Studies in a Large Family with Late‐Onset Alzheimer Disease (LOAD)
Studies in a Large Family with Late‐Onset Alzheimer Disease (LOAD)
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对患有晚发性阿尔茨海默病 (LOAD) 的大家庭的研究
DOI：
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发表时间：
1997
影响因子：
2.1
通讯作者：
Digamber S. Borgaonkar
中科院分区：
文献类型：
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作者：
E. Martin;S. E. Martin;L. Edelsohn;Digamber S. Borgaonkar
对一个10代晚发性阿尔茨海默病(LOAD)常染色体显性遗传大家族进行了历史、临床和遗传学评估。这个家族的起源可以追溯到一对法国血统的创始人夫妇，他们有大约3000名后代。虽然遗传易感性是通过男性个体传播的，但观察到受影响的女性占主导地位。目前，有14人被归类为阿尔茨海默病患者，其中12人为女性。受影响的患者中，发病年龄从55岁到78岁不等。载脂蛋白E(APOE)基因座的基因分型显示，E4等位基因(APOE4)的纯合子在60岁后期出现AD症状，而受影响的杂合子在70多岁时出现AD症状。患病家系成员的载脂蛋白E4频率显著高于未患病者(0.79vs.0.25，X2=9.919，p=0.0016，df=1)。许多患者在确诊发病后存活了15年以上，这可以归因于环境的改善，包括在疾病致残阶段的出色护理和管理。或者，这可能是阿尔茨海默病遗传异质性的一个例子。完整的大家族记录将有助于发现阿尔茨海默病发病机制中的多种遗传因素。
A large 10-generation family with late-onset Alzheimer disease (LOAD) inherited as an autosomal dominant trait was evaluated historically, clinically, and genetically. The family origin was traced to a founder couple of French ancestry with approximately 3,000 descendants. Although the transmission of a genetic predisposition to LOAD is demonstrated through male individuals, a predominance of affected women is observed. Currently, 14 individuals, 12 of whom are women, are classified as affected with Alzheimer disease (AD). Among the affected, the age of onset ranged from 55 to 78 years. Geno-typing of the apolipoprotein E (APOE) locus demonstrated that homozygotes for the E4 allele (APOE4) developed signs of AD in their late 60s, whereas affected heterozygotes presented with the disease in their 70s. A significantly higher APOE4 frequency was observed in affected family members than in those unaffected (0.79 vs. 0.25, X2 = 9.919, p = 0.0016, df = 1). Survival for more than 15 years after diagnosed onset was observed in a number of those affected and can be attributed to an improved environment, including excellent care and management during the disabling phase of illness. Alternatively, it may be an example of the genetic heterogeneity in AD. Complete documentation of large families such as the one presented will facilitate the discovery of the multiple genetic factors involved in the pathogenesis of AD.