Apolipoprotein E ε4 allele, AD pathology, and the clinical expression of Alzheimer's disease
Apolipoprotein E ε4 allele, AD pathology, and the clinical expression of Alzheimer's disease
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DOI：
10.1212/01.wnl.0000042478.08543.f7
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发表时间：
2003-01-28
期刊：
影响因子：
9.9
通讯作者：
Bienias, JL
中科院分区：
文献类型：
--
作者：
Bennett, DA;Wilson, RS;Bienias, JL
目的：验证APOE ε 4等位基因通过与疾病的病理标志相关而与AD的临床表现相关的假设。研究方法：参与者是年长的天主教修女，牧师和兄弟，他们同意每年对AD和其他常见的神经系统疾病进行神经学和神经心理学评估，并在死亡时进行大脑尸检。有77人没有痴呆症，51人可能患有AD; 38名参与者有一个或多个ε 4等位基因。结果如下：在logistic回归分析中，控制了年龄、性别和教育，ε 4等位基因与临床AD的可能性密切相关（比值= 3.46，95%CI = 1.44至8.33）。然而，控制AD病理学的影响，E等位基因与临床AD的关联降低了>50%，并且不再显著（优势= 1.58，95%CI = 0.56至4.43）。同样，在控制年龄、性别和教育程度的线性回归分析中，epsilon 4等位基因与死亡前的认知功能水平密切相关（回归系数=-0.477，p = 0.005）。然而，在控制了AD病理学的影响后，ε 4等位基因与认知水平的关联降低了>80%并且不再显著（回归系数= -0.093）。在使用单独测量神经炎性斑块、弥漫性斑块和神经纤维缠结的分析中，以及在五种不同认知系统（情景记忆、语义记忆、工作记忆、感知速度和视觉空间能力）的分析中，发现了类似的结果。结论：APOE ε 4等位基因似乎通过与AD的病理标志相关而不是通过其他机制与AD的临床表现相关。
Objective: To test the hypothesis that the APOE epsilon4 allele is associated with the clinical manifestations of AD through an association with the pathologic hallmarks of disease. Methods: Participants were older Catholic nuns, priests, and brothers who agreed to annual neurologic and neuropsychological evaluation for AD and other common neurologic conditions and brain autopsy at the time of death. There were 77 persons without dementia and 51 with probable AD; 38 participants had one or more epsilon4 alleles. Results: In logistic regression analyses, controlling for age, sex, and education, the epsilon4 allele was strongly associated with the likelihood of clinical AD (odds = 3.46, 95% CI = 1.44 to 8.33). However, controlling for the effect of AD pathology, the association of the E allele with clinical AD was reduced by >50% and was no longer significant (odds = 1.58, 95% CI = 0.56 to 4.43). Similarly, in linear regression analyses, controlling for age, sex, and education, the epsilon4 allele was strongly associated with level of cognitive function proximate to death (regression coefficient = -0.477, p = 0.005). However, after controlling for the effect of AD pathology, the association of the epsilon4 allele with level of cognition was reduced by >80% and was no longer significant (regression coefficient = -0.093). Similar results were found in analyses using separate measures of neuritic plaques, diffuse plaques, and neurofibrillary tangles, and in analyses of five different cognitive systems (episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability). Conclusions: The APOE epsilon4 allele appears to be associated with the clinical manifestations of AD through an association with the pathologic hallmarks of AD rather than another mechanism.