Breitner J C, Welsh K A, Gau B A, McDonald W M, Steffens D C, Saunders A M, Magruder K M, Helms M J, Plassman B L, Folstein M F
Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA.
Arch Neurol. 1995 Aug;52(8):763-71. doi: 10.1001/archneur.1995.00540320035011.
To detect cases of Alzheimer's disease (AD) in a large population of twins living throughout the United States and to examine concordance for AD in twins as a function of age and genotype for apolipoprotein E (APOE).
Nationwide survey.
Multistage screening and field evaluation beginning with two telephone interviews and culminating with laboratory tests, longitudinal neuropsychological measures, physician examination, and diagnostic consensus among experts.
Membership in 1990-1991 of intact pairs in the National Academy of Sciences--National Research Council Registry of veteran twins, then aged 62 to 73 years.
Completeness of case detection was examined in collateral studies. Zygosity and APOE genotypes were determined by restriction mapping. Concordance was calculated by the proband method.
Ninety subjects who screened positively for AD were studied in person, and 60 whose differential diagnoses included AD were followed up, as were their co-twins. Sensitivity of screening was estimated at greater than 99%, but 24% of subjects refused participation after initial screening. Seven of 38 diagnoses of AD have been confirmed at autopsy, and 31 other subjects eventually met criteria for probable or possible AD (prevalence estimate, 0.42%, 95% confidence interval, 0.29% to 0.56%), with good interrater reliability (intraclass r = .86). Excluding one discordant pair with unknown zygosity, concordance rates were 21.1% (4/19) for monozygotic and 11.1% (2/18) for dizygotic probands. Concordance was 50% for twins sharing the epsilon 4/epsilon 4 genotype at APOE, but there were no affected co-twins of 15 probands with onset before age 70 years, no epsilon 4 allele, and no family history of AD. The mean (SD) period of discordance in the latter pairs was 11.3 (3.3) years.
The multistage case-detection approach achieved reliable and valid diagnoses of AD with high apparent sensitivity but substantial attrition after initial screening. Genetic influences in AD at this age are limited, except among homozygotes for allele epsilon 4 at APOE. Subjects with early-onset AD who lack the epsilon 4 allele are not rare, and their condition appears to have little genetic influence. They should be ideal for studies on environmental cause of AD.
在美国各地生活的大量双胞胎群体中检测阿尔茨海默病（AD）病例，并研究双胞胎中AD的一致性与年龄及载脂蛋白E（APOE）基因型的关系。
全国性调查。
多阶段筛查和现场评估，始于两次电话访谈，最终进行实验室检测、纵向神经心理学测量、医生检查以及专家之间的诊断共识。
1990 - 1991年美国国家科学院 - 国家研究委员会退伍军人双胞胎登记处中年龄在62至73岁的完整双胞胎对。
在附带研究中检查病例检测的完整性。通过限制性图谱确定合子性和APOE基因型。采用先证者法计算一致性。
对90名AD筛查呈阳性的受试者进行了亲自研究，对60名鉴别诊断包括AD的受试者及其双胞胎进行了随访。筛查的敏感性估计大于99%，但24%的受试者在初次筛查后拒绝参与。38例AD诊断中有7例已通过尸检证实，另外31名受试者最终符合可能或疑似AD的标准（患病率估计为0.42%，95%置信区间为0.29%至0.56%），评分者间信度良好（组内相关系数r = 0.86）。排除一对合子性未知的不一致双胞胎对后，同卵双胞胎先证者的一致性率为21.1%（4/19），异卵双胞胎先证者的一致性率为11.1%（2/18）。APOE基因位点为ε4/ε4基因型的双胞胎一致性为50%，但15名发病年龄在70岁之前、无ε4等位基因且无AD家族史的先证者没有受影响的双胞胎。后一组双胞胎不一致的平均（标准差）时间为11.3（3.3）年。
多阶段病例检测方法实现了对AD可靠有效的诊断，具有较高的表面敏感性，但初次筛查后有大量受试者流失。在这个年龄段，AD的遗传影响有限，APOE基因ε4等位基因纯合子除外。缺乏ε4等位基因的早发性AD患者并不罕见，且其病情似乎几乎没有遗传影响。他们应是AD环境病因研究的理想对象。
