Gladstone Institute of Neurological Disease, Department of Pathology, University of California, San Francisco, CA 94158, USA.
Biochem Soc Trans. 2011 Aug;39(4):924-32. doi: 10.1042/BST0390924.
ApoE4 (apolipoprotein E4) is the major known genetic risk factor for AD (Alzheimer's disease). In most clinical studies, apoE4 carriers account for 65-80% of all AD cases, highlighting the importance of apoE4 in AD pathogenesis. Emerging data suggest that apoE4, with its multiple cellular origins and multiple structural and biophysical properties, contributes to AD in multiple ways either independently or in combination with other factors, such as Aβ (amyloid β-peptide) and tau. Many apoE mouse models have been established to study the mechanisms underlying the pathogenic actions of apoE4. These include transgenic mice expressing different apoE isoforms in neurons or astrocytes, those expressing neurotoxic apoE4 fragments in neurons and human apoE isoform knock-in mice. Since apoE is expressed in different types of cells, including astrocytes and neurons, and in brains under diverse physiological and/or pathophysiological conditions, these apoE mouse models provide unique tools to study the cellular source-dependent roles of apoE isoforms in neurobiology and in the pathogenesis of AD. They also provide useful tools for discovery and development of drugs targeting apoE4's detrimental effects.
载脂蛋白 E4（ApoE4）是 AD（阿尔茨海默病）的主要已知遗传风险因素。在大多数临床研究中，载脂蛋白 E4 携带者占所有 AD 病例的 65-80%，这突出了载脂蛋白 E4 在 AD 发病机制中的重要性。新出现的数据表明，载脂蛋白 E4 具有多种细胞起源和多种结构和物理特性，通过独立或与其他因素（如 Aβ（淀粉样 β 肽）和 tau）相结合，以多种方式促进 AD 的发生。已经建立了许多载脂蛋白 E 小鼠模型来研究载脂蛋白 E4 致病作用的机制。这些模型包括在神经元或星形胶质细胞中表达不同载脂蛋白 E 同工型的转基因小鼠、在神经元中表达神经毒性载脂蛋白 E4 片段和人类载脂蛋白 E 同工型敲入小鼠。由于载脂蛋白 E 在不同类型的细胞（包括星形胶质细胞和神经元）以及在不同生理和/或病理生理条件下的大脑中表达，这些载脂蛋白 E 小鼠模型为研究载脂蛋白 E 同工型在神经生物学和 AD 发病机制中的细胞来源依赖性作用提供了独特的工具。它们还为发现和开发针对载脂蛋白 E4 有害影响的药物提供了有用的工具。
