Association of apolipoprotein E allele €4 with late-onset familial and sporadic Alzheimer’s disease
Association of apolipoprotein E allele €4 with late-onset familial and sporadic Alzheimer’s disease
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发表时间：
2006
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通讯作者：
PhD A.M. Saunders;MD W.J. Strittmatter;MD D. Schmechel;P. H. St;MD M.A George-Hyslop;PhD S.H Pericak-Vance-PhD-S.H
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作者：
PhD A.M. Saunders;MD W.J. Strittmatter;MD D. Schmechel;P. H. St;MD M.A George-Hyslop;PhD S.H Pericak-Vance-PhD-S.H
文章摘要-载脂蛋白E，€4型等位基因（APOE ~ 4），与迟发性家族性阿尔茨海默病（AD）相关。淀粉样蛋白P-肽与ApoE蛋白具有高亲合力和特异性结合。为了验证晚发型家族性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 α 4与一系列可能的散发性AD患者显著相关（AD患者为0.36 f 0.042，对照组为0.16 k 0.027 [等位基因频率估计f标准误]，p = 0.00031）。配偶对照与来自人类多态性研究中心（CEPH）或文献对照的CEPH祖父母对照没有差异。大量尸检记录艾德散发性AD患者的组合系列也证明与APOE α 4等位基因高度显著相关（0.40 f 0.026，p 5 0.00001）。这些数据支持ApoE 4参与迟发性家族性和散发性AD的发病机制。ApoE亚型可能在P-肽代谢中起重要作用，APOE α 4可能作为AD临床表现的易感基因（危险因素）。
Article abstract-Apolipoprotein E, type €4 allele (APOE ~ 4 ) , is associated with late-onset familial Alzheimer’s disease (AD). There is high avidity and specific binding of amyloid P-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 €4 is significantly associated with a series of probable sporadic AD patients (0.36 f 0.042, AD, versus 0.16 k 0.027, controls [allele frequency estimate f 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-document-ed sporadic AD patients also demonstrated highly significant association with the APOE €4 allele (0.40 f 0.026, p 5 0.00001). These data support the involvement of ApoE €4 in the pathogenesis of late-onset familial and sporadic AD. ApoE isoforms may play an important role in the metabolism of p-peptide, and APOE €4 may operate as a susceptibility gene (risk factor) for the clinical expression of AD.