ASSOCIATION OF APOLIPOPROTEIN-E ALLELE EPSILON-4 WITH LATE-ONSET FAMILIAL AND SPORADIC ALZHEIMERS-DISEASE
ASSOCIATION OF APOLIPOPROTEIN-E ALLELE EPSILON-4 WITH LATE-ONSET FAMILIAL AND SPORADIC ALZHEIMERS-DISEASE
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DOI：
10.1212/wnl.43.8.1467
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发表时间：
1993-08-01
期刊：
影响因子：
9.9
通讯作者：
ROSES, AD
中科院分区：
文献类型：
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作者：
SAUNDERS, AM;STRITTMATTER, WJ;ROSES, AD
载脂蛋白E，epsilon4型等位基因(ApoE Epsilon4)与晚发性家族性阿尔茨海默病(AD)相关。淀粉样β蛋白与载脂蛋白E有很高的亲和力和特异性结合。为了验证晚发性家族性AD可能代表散发性AD在足够大的家族中聚集的假设，我们将APOE等位基因的分析扩展到几个系列的散发性AD患者。ApoE epsil4与一系列可能的散发性AD患者显著相关(0.36+/-0.042，AD，与0.16+/-0.027，对照[等位基因频率估计+/-标准差]，p=0.00031)。配偶对照与CEPH祖父母对照、人类多态中心(CEPH)对照或文献对照没有不同。大量尸检记录的散发性AD患者也显示与apoE epsilon4等位基因高度相关(0.40+/-0.026，p小于或等于-0.00001)。这些数据支持载脂蛋白E epsilon 4参与晚发性家族性和散发性AD的发病机制。APOE亚型可能在β-肽代谢中起重要作用，APOE epsilon 4可能是AD临床表现的易感基因(危险因子)。
Apolipoprotein E, type epsilon4 allele (APOE epsilon4), is associated with late-onset familial Alzheimer's disease (AD). There is high avidity and specific binding of amyloid beta-peptide with the protein ApoE. To test the hypothesis that late-onset familial AD may represent the clustering of sporadic AD in families large enough to be studied, we extended the analyses of APOE alleles to several series of sporadic AD patients. APOE epsilon4 is significantly associated with a series of probable sporadic AD patients (0.36 +/- 0.042, AD, versus 0.16 +/- 0.027, controls [allele frequency estimate +/-standard error], p = 0.00031). Spouse controls did not differ from CEPH grandparent controls from the Centre d'Etude du Polymorphisme Humain (CEPH) or from literature controls. A large combined series of autopsy-documented sporadic AD patients also demonstrated highly significant association with the APOE epsilon4 allele (0.40 +/- 0.026, p less-than-or-equal-to 0.00001). These data support the involvement of ApoE epsilon4 in the pathogenesis of late-onset familial and sporadic AD. ApoE isoforms may play an important role in the metabolism of beta-peptide, and APOE epsilon4 may operate as a susceptibility gene (risk factor) for the clinical expression of AD.