Higgins G A, Large C H, Rupniak H T, Barnes J C
Neurosciences Unit, Glaxo Wellcome Medicines Research Centre, Stevenage, Hertfordshire, UK.
Pharmacol Biochem Behav. 1997 Apr;56(4):675-85. doi: 10.1016/s0091-3057(96)00420-0.
There are three isoforms of the 33-kDa protein apolipoprotein E (apoE), termed apoE2, apoE3, and apoE4, each encoded by distinct genes APOE2, APOE3 and APOE4, respectively. In 1993, the APOE genotype was identified as a risk factor for Alzheimer's disease (AD) and was subsequently acknowledged to account for approximately 60% of all cases. The influence of the APOE genotype in AD is clearly isoform dependent, APOE4 imparting susceptibility and APOE2 protection. Thus, patients homozygous for the E4 allele show a very strong likelihood of developing the disease by age 75, whereas patients carrying at least one E2 allele are unlikely to develop symptoms of AD by this age. A major issue in AD research is therefore to understand the functional differences between the ApoE isoforms, with the ultimate aim of designing the next generation of drugs to treat this disease. The purpose of the present article is to summarise some of this work. This review encompasses the rapidly developing molecular, cellular and behavioural research into ApoE, and attempts to highlight those findings we consider to be of particular significance.
33千道尔顿的载脂蛋白E（apoE）有三种异构体，分别称为apoE2、apoE3和apoE4，它们分别由不同的基因APOE2、APOE3和APOE4编码。1993年，APOE基因型被确定为阿尔茨海默病（AD）的一个风险因素，随后被认为约占所有病例的60%。APOE基因型在AD中的影响显然依赖于异构体，APOE4会增加易感性，而APOE2则具有保护作用。因此，E4等位基因纯合的患者在75岁时患该病的可能性非常大，而携带至少一个E2等位基因的患者在这个年龄不太可能出现AD症状。因此，AD研究中的一个主要问题是了解ApoE异构体之间的功能差异，最终目标是设计出治疗这种疾病的下一代药物。本文的目的是总结其中的一些工作。这篇综述涵盖了对ApoE迅速发展的分子、细胞和行为研究，并试图突出那些我们认为特别重要的发现。
