The accumulation of neurotoxic amyloid-beta (Aβ) in the brain is a characteristic of Alzheimer's disease (AD), at the same time, it is possible alterations of liver function could affect brain Aβ levels through changes in blood Aβ concentration. Over the last decade, a number of reports have shown that P-glycoprotein (encoded by ABC1B1) actively mediates the efflux transport of Aβ peptides. However, the mechanism by which Aβ peptides enter the cells is not clear. In the preliminary study, we found that the protein expression of organic anion transporting Polypeptide 1a4 (OATP1B1) in the liver tissue of mice with AD was significantly higher than that in the normal mice. In contrast, the protein expression of Oatp1a4 in the brain significantly decreased in mice with AD. OATP1B1, an important drug transporter might be related to the pathophysiology of AD. In this study, we established an OATP1B1-GFP-HEK293T cell model to confirm the OATP1B1 mediated transport of Aβ1-42. Compared to the control group of GFP-HEK293Tcells, the uptake of Aβ1-42 protein in the OATP1B1-GFP-HEK293T group increased significantly with the increase in concentration of Aβ1-42, and also increased significantly with an increase in the duration of incubation. Similar results were observed in the flow cytometry experiment, and the uptake of Aβ1-42in HEK293T-OATP1B1 cells was almost twice that in the control group. These results indicate that OATPs may act as an important “carrier” for the transport of Aβ1-42 from the blood to the tissues, including liver and brain. This is a novel and interesting finding and OATP1B1 can be investigated as a new treatment target for AD.

中文翻译：

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OATPs对Aβ的摄取可能是阿尔茨海默病的新病理生理机制

大脑中神经毒性淀粉样蛋白 (Aβ) 的积累是阿尔茨海默病 (AD) 的一个特征，同时，肝功能的改变可能会通过血液 Aβ 浓度的变化影响大脑的 Aβ 水平。在过去十年中，许多报告表明 P-糖蛋白（由 ABC1B1 编码）主动介导 Aβ 肽的外排转运。然而，Aβ肽进入细胞的机制尚不清楚。在初步研究中，我们发现有机阴离子转运多肽1a4（OATP1B1）在AD小鼠肝组织中的蛋白表达明显高于正常小鼠。相比之下，AD 小鼠大脑中 Oatp1a4 的蛋白质表达显着降低。OATP1B1, 一种重要的药物转运蛋白可能与 AD 的病理生理学有关。在本研究中，我们建立了 OATP1B1-GFP-HEK293T 细胞模型以确认 OATP1B1 介导的 Aβ1-42 转运。与GFP-HEK293T细胞对照组相比，OATP1B1-GFP-HEK293T组对Aβ1-42蛋白的摄取随着Aβ1-42浓度的增加而显着增加，并且随着孵育时间的增加也显着增加。在流式细胞仪实验中也观察到类似的结果，Aβ1-42在HEK293T-OATP1B1细胞中的摄取几乎是对照组的两倍。这些结果表明，OATPs 可以作为 Aβ1-42 从血液转运到包括肝脏和大脑在内的组织的重要“载体”。