淀粉样蛋白(真菌学)
神经退行性变
脑淀粉样血管病
淀粉样前体蛋白
表型
突变
β淀粉样蛋白
阿尔茨海默病
转基因小鼠
作者
Lotta E. Oikari,Rucha Pandit,Romal Stewart,Carla Cuni-Lopez,Hazel Quek,Ratneswary Sutharsan,Laura M. Rantanen,Minna Oksanen,Šárka Lehtonen,Carmela Maria de Boer,Jose M. Polo,Jürgen Götz,Jari Koistinaho,Anthony R. White
标识
DOI:10.1016/j.stemcr.2020.03.011
摘要
The blood-brain barrier (BBB) presents a barrier for circulating factors, but simultaneously challenges drug delivery. How the BBB is altered in Alzheimer disease (AD) is not fully understood. To facilitate this analysis, we derived brain endothelial cells (iBECs) from human induced pluripotent stem cells (hiPSCs) of several patients carrying the familial AD PSEN1 mutation. We demonstrate that, compared with isogenic PSEN1 corrected and control iBECs, AD-iBECs exhibit altered tight and adherens junction protein expression as well as efflux properties. Furthermore, by applying focused ultrasound (FUS) that transiently opens the BBB and achieves multiple therapeutic effects in AD mouse models, we found an altered permeability to 3-5 kDa dextran as a model cargo and the amyloid-β (Aβ) peptide in AD-iBECs compared with control iBECs. This presents human-derived in vitro models of the BBB as a valuable tool to understand its role and properties in a disease context, with possible implications for drug delivery.
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