Apolipoprotein E ε4 count affects age at onset of Alzheimer disease, but not lifetime susceptibility -: The cache county study
Apolipoprotein E ε4 count affects age at onset of Alzheimer disease, but not lifetime susceptibility -: The cache county study
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DOI：
10.1001/archpsyc.61.5.518
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发表时间：
2004-05-01
影响因子：
--
通讯作者：
Breitner, JCS
中科院分区：
文献类型：
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作者：
Khachaturian, AS;Corcoran, CD;Breitner, JCS
背景资料：阿尔茨海默病（AD）的发病率随着年龄的增长而显著增加，但对AD在100年的累积发病率及其与编码载脂蛋白E的多态性APOE基因座的关系知之甚少。APOE是AD的一个强遗传危险因子。目的：估计AD的发生率作为年龄和APOE ε 4等位基因数量的函数;并探索与APOE基因型和其他来源相关的AD风险异质性的证据。设计：前瞻性纵向研究中AD发病率的非参数和参数生存分析。设置和参与者：研究对象为犹他州Cache县的3308名老年居民。主要结果测量：AD的累积发病率;在混合模型中，假设易感和非易感个体，在任何年龄段对AD不易感的个体比例。结果：假设一定比例的无敌个体的模型提供了对数据的极大改进的拟合。这些模型估计AD的100年终生发病率为72%，这意味着28%的人在任何合理的预期寿命内都不会患上AD。我们证实了加速AD发病的个人与1或，特别是，2 APOE ε 4等位基因，但没有观察到有意义的差异，在100年的终身发病率相关的数量ε 4 allele.Conclusions：APOE ε 4等位基因作为一个有效的危险因素，为AD加速发病。然而，AD的风险似乎在独立于APOE的方式上是异质的。有些人似乎注定要逃脱AD，甚至在延长的寿命。它们的相对不受伤害性可能反映了其他可以研究的基因或环境因素。
Background: The incidence of Alzheimer disease (AD) increases strongly with age, but little is known about the cumulative incidence of AD over a lifetime of 100 years, or its relationship to the polymorphic APOE locus that encodes apolipoprotein E. APOE is a strong genetic risk factor for AD.Objectives: To estimate the occurrence of AD as a function of age and number of APOE epsilon4 alleles; and to explore evidence for heterogeneity of AD risk related to APOE genotype and to other sources.Design: Nonparametric and parametric survival analyses of AD incidence in prospective longitudinal study.Setting and Participants: A total of 3308 elderly residents of Cache County, Utah.Main Outcome Measures: Cumulative incidence of AD; in mixture models assuming susceptible and nonsusceptible individuals, the proportion of individuals not susceptible to AD at any age.Results: Models that assumed a proportion of invulnerable individuals provided strongly improved fit to the data. These models estimated the 100-year lifetime incidence of AD at 72%, implying that 28% of individuals would not develop AD over any reasonable life expectancy. We confirmed the acceleration of AD onset in individuals with 1 or, especially, 2 APOE epsilon4 alleles, but observed no meaningful difference in 100-year lifetime incidence related to number Of epsilon4 alleles.Conclusions: The APOE epsilon4 allele acts as a potent risk factor for AD by accelerating onset. However, the risk of AD appears heterogeneous in ways independent of APOE. Some individuals seem destined to escape AD, even over an extended lifespan. Their relative invulnerability may reflect other genes or environmental factors that can be investigated.