APOLIPOPROTEIN-E - HIGH-AVIDITY BINDING TO BETA-AMYLOID AND INCREASED FREQUENCY OF TYPE-4 ALLELE IN LATE-ONSET FAMILIAL ALZHEIMER-DISEASE
APOLIPOPROTEIN-E - HIGH-AVIDITY BINDING TO BETA-AMYLOID AND INCREASED FREQUENCY OF TYPE-4 ALLELE IN LATE-ONSET FAMILIAL ALZHEIMER-DISEASE
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DOI：
10.1073/pnas.90.5.1977
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发表时间：
1993-03-01
影响因子：
11.1
通讯作者：
ROSES, AD
中科院分区：
文献类型：
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作者：
STRITTMATTER, WJ;SAUNDERS, AM;ROSES, AD
载脂蛋白E免疫化学定位于阿尔茨海默病的老年斑、血管淀粉样蛋白和神经纤维缠结。在体外，脑脊液中的载脂蛋白E以高亲和力与合成的β A4肽（老年斑的主要成分）结合。需要β A4肽的氨基酸12-28。载脂蛋白E基因位于染色体19q13.2，在以前与迟发性家族性阿尔茨海默病连锁的区域内。载脂蛋白E等位基因在阿尔茨海默病和对照组的分析表明，载脂蛋白E 4型等位基因（APOE-ε 4）和迟发性家族性阿尔茨海默病有高度显着的关联。在30名随机患病的患者中，APOE-ε 4等位基因频率为0.50 +/- 0.06;在91名年龄匹配的无关对照中，APOE-ε 4等位基因频率为0.16 +/- 0.03（Z = 2.44，P = 0.014）。载脂蛋白E-E4亚型在迟发性家族性阿尔茨海默病发病机制中的功能作用。
Apolipoprotein E is immunochemically localized to the senile plaques, vascular amyloid, and neurofibrillary tangles of Alzheimer disease. In vitro, apolipoprotein E in cerebrospinal fluid binds to synthetic betaA4 peptide (the primary constituent of the senile plaque) with high avidity. Amino acids 12-28 of the betaA4 peptide are required. The gene for apolipoprotein E is located on chromosome 19q13.2, within the region previously associated with linkage of late-onset familial Alzheimer disease. Analysis of apolipoprotein E alleles in Alzheimer disease and controls demonstrated that there was a highly significant association of apolipoprotein E type 4 allele (APOE-epsilon4) and late-onset familial Alzheimer disease. The allele frequency of the APOE-epsilon4 in 30 random affected patients, each from a different Alzheimer disease family, was 0.50 +/- 0.06; the allele frequency of APOE-epsilon4 in 91 age-matched unrelated controls was 0.16 +/- 0.03 (Z = 2.44, P = 0.014). A functional role of the apolipoprotein E-E4 isoform in the pathogenesis of late-onset familial Alzheimer disease is suggested.