Kindy M S, Rader D J
Department of Biochemistry, University of Kentucky School of Medicine, and the Veterans Affairs Medical Center, Lexington 40536-0084, USA.
Am J Pathol. 1998 May;152(5):1387-95.
Apolipoproteins have been implicated in the formation of amyloid fibrils. Recent studies have demonstrated that apolipoprotein E (apoE), alone or in combination with apolipoprotein J (apoJ), and other lipoproteins appear to enhance deposition of amyloid fibrils both in systemic and cerebral amyloids, especially Alzheimer's disease (AD). ApoE enhanced the ability of the amyloid beta-protein (1-40) fragment (A beta) to form fibrils in vitro, with apoE4 promoting the greatest fibril formation. ApoE was found associated with both human and mouse amyloid A (AA) deposits. To define the role of apoE in vivo, we utilized mice lacking the apoE gene by gene targeting. We used the AA model in mice to characterize the function of the apoE protein in amyloid fibrillogenesis. ApoE-deficient mice exhibited a decrease in deposition of AA when compared with heterozygous mutant or wild-type animals. In addition, apoE-deficient mice that were injected with an adenovirus that expressed the human apoE3 gene had restored AA deposition and the apoE was associated with the AA fibrils. These results are agreement with the in vitro studies using the beta-peptide and suggest that apoE is not essential for amyloid fibrillogenesis but can promote the development of amyloid deposition.
载脂蛋白与淀粉样纤维的形成有关。最近的研究表明，载脂蛋白E（apoE）单独或与载脂蛋白J（apoJ）及其他脂蛋白结合，似乎会增强全身和脑淀粉样蛋白，尤其是阿尔茨海默病（AD）中淀粉样纤维的沉积。ApoE在体外增强了β淀粉样蛋白（1-40）片段（Aβ）形成纤维的能力，其中apoE4促进纤维形成的能力最强。人们发现ApoE与人及小鼠的淀粉样蛋白A（AA）沉积物有关。为了确定apoE在体内的作用，我们利用基因靶向技术培育出缺乏apoE基因的小鼠。我们使用小鼠AA模型来研究apoE蛋白在淀粉样纤维形成过程中的功能。与杂合突变体或野生型动物相比，缺乏apoE的小鼠AA沉积减少。此外，给缺乏apoE的小鼠注射表达人apoE3基因的腺病毒后，AA沉积得以恢复，且apoE与AA纤维有关。这些结果与使用β肽的体外研究结果一致，表明apoE对淀粉样纤维形成并非必不可少，但可促进淀粉样沉积物的形成。
