J Clin Invest. 2018 May 1;128(5):1734-1736. doi: 10.1172/JCI120414. Epub 2018 Mar 30.
Inheritance of the E4 allele of the apolipoprotein E gene (APOE4) substantially increases the risk of developing late-onset Alzheimer disease (AD). A large body of evidence has firmly established a role for apoE in modulating the risk of developing the amyloid plaque pathology that is pathognomonic for AD. In this issue of the JCI, Liao and colleagues discovered that antibodies against a nonlipidated form of apoE4 are highly effective in delaying the deposition of amyloid β (Aβ) peptides in mouse models of AD pathology. Using a combination of passive immunization and viral-mediated expression of recombinant antibodies, the authors show that Fc receptor-mediated clearance of the nonlipidated apoE4 was critical in delaying Aβ deposition. Collectively, this study identifies a new therapeutic target that could be exploited to prevent, or possibly reverse, the Aβ pathology of AD.
载脂蛋白 E 基因（APOE4）的 E4 等位基因遗传大大增加了发生晚发性阿尔茨海默病（AD）的风险。大量证据已确凿无疑地确立了载脂蛋白 E 在调节发生淀粉样斑块病理的风险中的作用，而淀粉样斑块病理是 AD 的特征性病理。在本期 JCI 中，Liao 及其同事发现针对载脂蛋白 E4 的非脂化形式的抗体在 AD 病理的小鼠模型中非常有效地延迟了淀粉样 β（Aβ）肽的沉积。作者使用被动免疫和病毒介导的重组抗体表达的组合，表明 Fc 受体介导的非脂化载脂蛋白 E4 的清除对于延迟 Aβ沉积至关重要。总的来说，这项研究确定了一个新的治疗靶点，该靶点可被利用来预防或可能逆转 AD 的 Aβ病理。
