Campion D, Martinez M, Hannequin D, Brice A, Thomas-Anterion C, Michon A, Babron M C, Dubois B, Goas Y, Jaillard-Serradt A
Unité de Recherche d'Epidémiologie Génétique (INSERM U 155) Paris, France.
Am J Med Genet. 1995 Jun 19;60(3):221-7. doi: 10.1002/ajmg.1320600310.
Characteristics of familial aggregation of Alzheimer's Disease were studied in 92 families ascertained through a clinically diagnosed proband with an onset below age 60 years. In each family data were systematically collected on the sibships of the proband, of his father, and of his mother. A total of 926 relatives were included and 81% of the living relatives (i.e., 251 individuals) were directly examined. The estimated cumulative risk among first degree relatives was equal to 35% by age 89 years (95% confidence interval 22 to 47%). This result does not support the hypothesis that an autosomal dominant gene, fully penetrant by age 90 years, is segregating within all these pedigrees. Despite the fact that all probands were selected for an onset before age 60 years it was shown that two types of families could be delineated with respect to age at onset among affected relatives: all secondary cases with an onset below age 60 years were contributed by a particular group of families (type 1 families), whereas all secondary cases with an onset after age 60 years were contributed by another group of families (type 2 families). Although genetic interpretation of these findings is not straightforward, they support the hypothesis of etiologic heterogeneity in the determination of early-onset Alzheimer's disease.
对92个家庭中阿尔茨海默病的家族聚集特征进行了研究，这些家庭是通过临床诊断出发病年龄低于60岁的先证者确定的。在每个家庭中，系统收集了先证者及其父亲和母亲的同胞关系数据。总共纳入了926名亲属，其中81%的在世亲属（即251人）接受了直接检查。到89岁时，一级亲属的估计累积风险为35%（95%置信区间为22%至47%）。这一结果不支持这样的假设，即一个在90岁时完全显性的常染色体显性基因在所有这些家系中进行分离。尽管所有先证者都是因发病年龄在60岁之前而被选中的，但结果显示，就受影响亲属的发病年龄而言，可以划分出两种类型的家庭：所有发病年龄低于60岁的继发病例都来自特定的一组家庭（1型家庭），而所有发病年龄在60岁之后的继发病例则来自另一组家庭（2型家庭）。虽然对这些发现的遗传学解释并不简单，但它们支持了早发性阿尔茨海默病病因异质性的假设。
