Saunders A M, Hulette O, Welsh-Bohmer K A, Schmechel D E, Crain B, Burke J R, Alberts M J, Strittmatter W J, Breitner J C, Rosenberg C
Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Department of Medicine (Neurology), Duke University Medical Center, Durham, North Carolina 27710, USA.
Lancet. 1996 Jul 13;348(9020):90-3. doi: 10.1016/s0140-6736(96)01251-2.
We aimed to determine the specificity, sensitivity, and predictive value of apolipoprotein E (APOE) genotyping in 67 consecutive patients with clinical diagnoses of sporadic Alzheimer's disease (AD) who underwent necropsy.
We studied patients who attended the Duke Memory Disorders Clinic and were diagnosed as having probable AD. These patients were followed up until they died. APOE genotyping was done during life in most cases, but in some brain tissue obtained at necropsy was used. Members of known AD families were excluded.
After neuropathological examination 57 (85%) of 67 of our patients were confirmed as having AD including all 43 who had at least one APOE-epsilon 4 allele. None of the patients found not to have AD carried an epsilon 4 allele. In this series, the specificity of the epsilon 4 allele was 100%, the sensitivity 75%, the positive predictive value 100%, and the negative predictive value 42%. In this necropsy-confirmed series, the epsilon 4/epsilon 4 genotype predicted AD with 100% accuracy. The epsilon 3/epsilon 4 and epsilon 2/epsilon 4 genotypes were also unexpectedly highly specific for AD.
Data from hundreds of necropsy-confirmed non-AD patients in other longitudinal necropsy series will allow the predictive value of APOE genotypes to be assessed with useful confidence limits.
我们旨在确定67例临床诊断为散发性阿尔茨海默病（AD）且接受尸检的连续患者中载脂蛋白E（APOE）基因分型的特异性、敏感性和预测价值。
我们研究了在杜克记忆障碍诊所就诊且被诊断为可能患有AD的患者。这些患者一直随访至死亡。大多数情况下在患者生前进行APOE基因分型，但在一些病例中使用尸检时获得的脑组织。已知AD家族的成员被排除。
经神经病理学检查，我们的67例患者中有57例（85%）被确诊患有AD，其中包括所有43例至少携带一个APOE-ε4等位基因的患者。所有未被发现患有AD的患者均未携带ε4等位基因。在这个系列中，ε4等位基因的特异性为100%，敏感性为75%，阳性预测值为100%，阴性预测值为42%。在这个经尸检确诊的系列中，ε4/ε4基因型预测AD的准确率为100%。ε3/ε4和ε2/ε4基因型对AD的特异性也出人意料地高。
来自其他纵向尸检系列中数百例经尸检确诊的非AD患者的数据，将有助于在有意义的置信区间内评估APOE基因型的预测价值。
