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

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2020 Apr 11

PMID 32275861

Citations 41

Authors

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

Jurgen Gotz

Jari Koistinaho

Anthony R White

Affiliations

Soon will be listed here.

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, 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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