Journal article

Altered Brain Endothelial Cell Phenotype from a Familial Alzheimer Mutation and Its Potential Implications for Amyloid Clearance and Drug Delivery

Lotta E Oikari, Rucha Pandit, Romal Stewart, Carla Cuni-Lopez, Hazel Quek, Ratneswary Sutharsan, Laura M Rantanen, Minna Oksanen, Sarka Lehtonen, Carmela Maria de Boer, Jose M Polo, Juergen Goetz, Jari Koistinaho, Anthony R White

Stem Cell Reports | CELL PRESS | Published : 2020

Abstract

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,..

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University of Melbourne Researchers

Grants

Awarded by NHMRC


Awarded by European Union


Funding Acknowledgements

We thank the Genomics Research Center (IHBI, QUT) for technical assistance. We also thank Dr Liyu Chen (Queensland Brain Institute) for additional technical assistance. This research was supported by QIMR Berghofer SEED grant (to L.E.O.), NHMRC Project grants APP1125796 (to A.R.W.), and GNT1145580 (to J.G.). A.R.W. is a recipient of an NHMRC Senior Research Fellowship (APP1118452). The project is supported through the Academy of Finland under the aegis of JPND-www.jpnd.eu--and European Union's Horizon 2020 research and innovation program under grant agreement no. 643417 (to J.K.).