Department of Medicine, National Research Counci, Institute of Neurobiology and Molecular Medicine, Rome, Italy.
J Alzheimers Dis. 2010;21(1):35-48. doi: 10.3233/JAD-2010-100009.
Apolipoprotein E (ApoE) plays a key role in lipid transport in the plasma and in the central nervous system through its interaction with members of the low-density lipoprotein receptor family. The three common isoforms of ApoE (ApoE2, ApoE3, and ApoE4) differ in their ability to perform neuronal maintenance and repair functions and differentially affect the risk of developing neurodegenerative disorders. The ApoE4 isoform is a strong genetic risk factor for Alzheimer's disease. Up-to-date knowledge about the structural and biophysical features of ApoE4 shed light on the molecular basis underlying the isoform-specific pathogenic role of ApoE4 and its contribution to AD pathology through several different mechanisms. ApoE4 impacts on amyloid-beta (Abeta) production, Abeta clearance, Abeta fibrillation, and tangle formation as well as on mitochondrial functions leading to neuronal toxicity and synaptic damage. This review summarizes the pathological cross talk between ApoE and Abeta peptide in Alzheimer's disease. Lastly, we examine emerging gene-based therapeutic approaches encompassing the use of ApoE and their potential opportunities to preventing or treating Alzheimer's disease.
载脂蛋白 E（ApoE）通过与低密度脂蛋白受体家族成员的相互作用，在血浆和中枢神经系统中发挥关键的脂质转运作用。ApoE 的三种常见亚型（ApoE2、ApoE3 和 ApoE4）在执行神经元维持和修复功能的能力上存在差异，并且不同程度地影响神经退行性疾病的发病风险。ApoE4 亚型是阿尔茨海默病的一个强烈遗传风险因素。关于 ApoE4 的结构和生物物理特征的最新知识阐明了该亚型特定的致病作用的分子基础，以及其通过几种不同机制对 AD 病理的贡献。ApoE4 影响淀粉样蛋白-β（Abeta）的产生、Abeta 的清除、Abeta 的纤维化和缠结的形成，以及导致神经元毒性和突触损伤的线粒体功能。本综述总结了阿尔茨海默病中 ApoE 和 Abeta 肽之间的病理串扰。最后，我们研究了新兴的基于基因的治疗方法，包括 ApoE 的使用及其预防或治疗阿尔茨海默病的潜在机会。
