Uptake of Aβ by OATPs Might Be a New Pathophysiological Mechanism of Alzheimer Disease

Background: The accumulation of neurotoxic amyloid-beta (Aβ) in the brain is a characteristic of Alzheimer's disease (AD). Over the last decade, a number of reports have shown that P-glycoprotein (encoded by ABCB1 ) actively mediates the efflux transport of Aβ peptides. However, the mechanism by which Aβ peptides enter the cells is not clear. We found that the protein expression oforganic anion transporting Polypeptide 2 (Oatp2) in the liver tissue of mice with AD was significantly higher than that in the normal mice. In contrast, the protein expression of Oatp2 in the brain significantly decreased in mice with AD. OATP1B1, an important drug transporter might be related to the pathophysiology of AD. ResultsIn this study, we established an OATP1B1-GFP-HEK293T cell model to confirm the OATP1B1 mediated transport ofAβ 1-42 .Compared to the control group of GFP-HEK293Tcells, the uptake of Aβ 1-42 protein in the OATP1B1-GFP-HEK293T group increased significantly with the increase in concentration of Aβ 1-42 , 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 Aβ 1-42 in HEK239T-OATP1B1 cells was almost twice that in the control group. These results indicate that OATP1B1 acts as an important “carrier” for the transport of Aβ 1-42 from the blood to the tissues, including liver and brain. ConclusionsThis is a novel and interesting finding and OATP1B1 can be investigated as a new treatment target for AD.