Hanson Angela J, Craft Suzanne, Banks William A
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Curr Pharm Des. 2015;21(1):114-20. doi: 10.2174/1381612820666141020164222.
The translation of promising preclinical treatments into effective drugs for Alzheimer's disease (AD) has been challenging. One of the most potent risk factors for sporadic AD is carrier status of the epsilon 4 allele of the apolipoprotein E gene (E4). E4 carriers show a differential response to several therapies which are being investigated as AD treatments, including acetylcholinesterase inhibitors and therapeutics with vascular and metabolic targets. The differential treatment responses of E4 carriers may partially explain why some treatments show a null effect in clinical trials. Understanding the reasons behind these responses is not only important for clinical practice, but may also help us elucidate mechanisms for this neurodegenerative disease.
将有前景的临床前治疗方法转化为治疗阿尔茨海默病（AD）的有效药物一直具有挑战性。散发性AD最有力的风险因素之一是载脂蛋白E基因（E4）的ε4等位基因的携带者状态。E4携带者对几种正在作为AD治疗方法进行研究的疗法表现出不同的反应，包括乙酰胆碱酯酶抑制剂以及针对血管和代谢靶点的治疗方法。E4携带者不同的治疗反应可能部分解释了为什么有些治疗方法在临床试验中显示出无效。了解这些反应背后的原因不仅对临床实践很重要，还可能有助于我们阐明这种神经退行性疾病的机制。
