Generation of a set of isogenic iPSC lines carrying all APOE genetic variants (Ɛ2/Ɛ3/Ɛ4) and knock-out for the study of APOE biology in health and disease

生成一组携带所有 APOE 基因变异 (Ɛ2/Ɛ3/Ɛ4) 和敲除的同源 iPSC 系,用于研究健康和疾病中的 APOE 生物学

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作者:Benjamin Schmid, Bjørn Holst, Christian Clausen, Lamiaa Bahnassawy, Peter Reinhardt, Margot H M Bakker, Eva Díaz-Guerra, Carlos Vicario, Pamela V Martino-Adami, Michaela Thoenes, Alfredo Ramirez, Klaus Fliessbach, Clara Grezella, Oliver Brüstle, Michael Peitz, Andreas Ebneth, Alfredo Cabrera-Socorro

Abstract

APOE genotype is the strongest genetic risk factor for Alzheimer's Disease (AD). The low degree of homology between mouse and human APOE is a concerning issue in preclinical models currently used to study the role of this gene in AD pathophysiology. A key objective of ADAPTED (Alzheimer's Disease Apolipoprotein Pathology for Treatment Elucidation and Development) project was to generate in vitro models that better recapitulate human APOE biology. We describe a new set of induced pluripotent stem cells (iPSC) lines carrying common APOE variants (Ɛ2, Ɛ3, and Ɛ3/Ɛ4) and a knock-out isogenic to the parental APOE Ɛ4/Ɛ4 line (UKBi011-A).

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