Strittmatter W J, Saunders A M, Schmechel D, Pericak-Vance M, Enghild J, Salvesen G S, Roses A D
Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710.
Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1977-81. doi: 10.1073/pnas.90.5.1977.
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 beta A4 peptide (the primary constituent of the senile plaque) with high avidity. Amino acids 12-28 of the beta A4 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-epsilon 4) and late-onset familial Alzheimer disease. The allele frequency of the APOE-epsilon 4 in 30 random affected patients, each from a different Alzheimer disease family, was 0.50 +/- 0.06; the allele frequency of APOE-epsilon 4 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.
载脂蛋白E在免疫化学上定位于阿尔茨海默病的老年斑、血管淀粉样蛋白和神经原纤维缠结中。在体外，脑脊液中的载脂蛋白E能与合成的β淀粉样蛋白4肽（老年斑的主要成分）高亲和力结合。β淀粉样蛋白4肽的12 - 28位氨基酸是必需的。载脂蛋白E基因位于19号染色体的13.2区，该区域先前与晚发性家族性阿尔茨海默病的连锁有关。对阿尔茨海默病患者和对照者的载脂蛋白E等位基因分析表明，载脂蛋白E4等位基因（APOE-ε4）与晚发性家族性阿尔茨海默病有高度显著的关联。来自不同阿尔茨海默病家族的30例随机患病患者中APOE-ε4的等位基因频率为0.50±0.06；91例年龄匹配的无关对照者中APOE-ε4的等位基因频率为0.16±0.03（Z = 2.44，P = 0.014）。提示载脂蛋白E-E4异构体在晚发性家族性阿尔茨海默病发病机制中起作用。
