The Department of Neurobiology, Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Alzheimers Dement. 2014 Nov;10(6):861-8. doi: 10.1016/j.jalz.2014.06.015. Epub 2014 Sep 10.
Brain pathology of Alzheimer's diseases (AD) and the genetics of autosomal dominant familial AD have been the "lamp posts" under which the AD field has been looking for therapeutic targets. Although this approach still remains valid, none of the compounds tested to date have produced clinically meaningful results. This calls for developing complementary therapeutic approaches and AD targets. The allele ε4 of apolipoprotein E4 (APOE ε4), is the most prevalent genetic risk factor for sporadic AD, and is expressed in more than half of the AD patients. However, in spite of its genetic prominence, the allele APOE ε4 and its corresponding protein product apoE4 have been understudied. We presently briefly discuss the reasons underlying this situation and review newly developed AD therapeutic approaches that target apoE4 and which pave the way for future studies.
阿尔茨海默病（AD）的大脑病理学和常染色体显性家族性 AD 的遗传学一直是 AD 领域寻找治疗靶点的“指路明灯”。尽管这种方法仍然有效，但迄今为止测试的化合物没有一种产生了有临床意义的结果。这就需要开发补充的治疗方法和 AD 靶点。载脂蛋白 E4（APOE ε4）的等位基因 ε4 是散发性 AD 最常见的遗传风险因素，超过一半的 AD 患者都有这种基因。然而，尽管其遗传作用显著，但 APOE ε4 等位基因及其相应的蛋白产物 apoE4 一直研究不足。我们目前简要讨论了造成这种情况的原因，并回顾了新开发的针对 apoE4 的 AD 治疗方法，为未来的研究铺平了道路。
