Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer's disease
Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer's disease
复制标题
DOI：
10.1056/nejm199802193380804
复制
发表时间：
1998-02-19
影响因子：
158.5
通讯作者：
Phelps, CH
中科院分区：
文献类型：
--
作者：
Mayeux, R;Saunders, AM;Phelps, CH
背景
载脂蛋白E（APOE）编码基因的ε4等位基因与阿尔茨海默病密切相关，但其在诊断中的价值仍不确定。
方法
我们回顾了2188例因痴呆评估而被转诊至26个阿尔茨海默病中心之一的患者的临床诊断以及尸检诊断结果。以病理确诊的阿尔茨海默病为标准，计算临床诊断或存在APOE ε4等位基因的敏感性和特异性。通过多变量分析得到的验前概率和验后概率以及绘制敏感性与假阳性率关系的受试者工作特征曲线来评估APOE基因型的附加价值。
结果
在2188例患者中，1833例临床诊断为阿尔茨海默病，其中1770例经尸检病理确诊。临床诊断为阿尔茨海默病的患者中有62%至少有一个APOE ε4等位基因，而病理确诊为阿尔茨海默病的患者中有65%至少有一个该等位基因。临床诊断的敏感性为93%，特异性为55%，而APOE ε4等位基因的敏感性和特异性分别为65%和68%。在符合阿尔茨海默病临床标准的患者中，加入APOE基因型信息使总体特异性提高到84%，尽管敏感性有所降低。在对年龄、临床诊断、性别和中心的差异进行调整后，多变量分析中特异性的提高仍具有统计学意义。
结论
APOE基因分型单独作为阿尔茨海默病的诊断试验，其敏感性和特异性均不足，但与临床标准联合使用时，可提高诊断的特异性。（1998年，马萨诸塞州医学协会）
Background The epsilon 4 allele of the gene encoding apolipoprotein E (APOE) is strongly associated with Alzheimer's disease, but its value in the diagnosis remains uncertain.Methods We reviewed clinical diagnoses and diagnoses obtained at autopsy in 2188 patients referred to 1 of 26 Alzheimer's disease centers for evaluation of dementia. The sensitivity and specificity of the clinical diagnosis or the presence of an APOE epsilon 4 allele were calculated, with pathologically confirmed Alzheimer's disease used as the standard, The added value of the APOE genotype was estimated with pretest and post-test probabilities from multivariate analyses to gene rare receiver-operating-characteristic curves plotting sensitivity against the false positive rate.Result's Of the 2188 patients, 1833 were given a clinical diagnosis of Alzheimer's disease, and The diagnosis was confirmed pathologically in 1770 patients at autopsy. Sixty-two percent of patients with clinically diagnosed Alzheimer's disease, as compared with 65 percent of those with pathologically confirmed Alzheimer's disease, had at least one APOE epsilon 4 allele, The sensitivity of the clinical diagnosis was 93 percent, and the specificity was 55 percent, whereas the sensitivity and specificity of the APOE epsilon E4 allele were 65 and 68 percent, respectively. The addition of: information about the APOE genotype increased the overall specificity to 84 percent in patients who met the clinical criteria for Alzheimer's disease, although the sensitivity decreased, The improvement in specificity remained statistically significant in the multivariate analysis after adjustment for differences in age, clinical diagnosis, sex, and center.Conclusions APOE genotyping does not provide sufficient sensitivity or specificity to be used alone as a diagnostic test ibr Alzheimer's disease, but when used in combination with clinical criteria, it improves the specificity of the diagnosis, (C) 1998, Massachusetts Medical Society.