Strittmatter W J, Roses A D
Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, North Carolina, 27710, USA.
Annu Rev Neurosci. 1996;19:53-77. doi: 10.1146/annurev.ne.19.030196.000413.
The apolipoprotein E locus (APOE) is associated with variations in the age of onset and risk of Alzheimer's disease. The APOE4 allele increases the probability of disease at an earlier age. In contrast, the APOE3 and APOE2 alleles decrease the probability of disease and increase the age of onset. Therefore the metabolism of apolipoprotein E is relevant to Alzheimer's disease. Isoform-specific interactions of apolipoprotein E with other molecules may determine the rate of disease expression through molecular pathways that appear unique to the disease. In addition, some isoform-specific interactions of apolipoprotein E have been demonstrated with the defining pathological lesions of Alzheimer's disease, the neurofibrillary tangle and neuritic plaque. Several hypotheses of disease pathogenesis are now based on the relevance of apolipoprotein E.
载脂蛋白E基因座(APOE)与阿尔茨海默病的发病年龄和风险变化相关。APOE4等位基因增加了在较早年龄发病的可能性。相比之下,APOE3和APOE2等位基因降低了发病的可能性并提高了发病年龄。因此,载脂蛋白E的代谢与阿尔茨海默病相关。载脂蛋白E与其他分子的异构体特异性相互作用可能通过该疾病特有的分子途径决定疾病表达的速率。此外,已证实载脂蛋白E的一些异构体特异性相互作用与阿尔茨海默病的典型病理病变、神经原纤维缠结和神经炎性斑块有关。现在,几种疾病发病机制的假说是基于载脂蛋白E的相关性。