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

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 Flissbach; Clara Grezella; Oliver Brüstle; Michael Peitz; Andreas Ebneth; Alfredo Cabrera-Socorro

Stem Cell Research (Apr 2021)

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

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 Flissbach,
Clara Grezella,
Oliver Brüstle,
Michael Peitz,
Andreas Ebneth,
Alfredo Cabrera-Socorro

Affiliations

Benjamin Schmid: Bioneer A/S, Kogle Allé 2, 2970 Hørsholm, Denmark
Bjørn Holst: Bioneer A/S, Kogle Allé 2, 2970 Hørsholm, Denmark
Christian Clausen: Bioneer A/S, Kogle Allé 2, 2970 Hørsholm, Denmark
Lamiaa Bahnassawy: AbbVie Deutschland GmbH & Co.KG, Neuroscience Discovery, Knollstrasse, 67061 Ludwigshafen, Germany
Peter Reinhardt: AbbVie Deutschland GmbH & Co.KG, Neuroscience Discovery, Knollstrasse, 67061 Ludwigshafen, Germany
Margot H.M. Bakker: AbbVie Deutschland GmbH & Co.KG, Neuroscience Discovery, Knollstrasse, 67061 Ludwigshafen, Germany
Eva Díaz-Guerra: Cajal Institute-CSIC and CIBERNED-ISCIII, Madrid, Spain
Carlos Vicario: Cajal Institute-CSIC and CIBERNED-ISCIII, Madrid, Spain
Pamela V. Martino-Adami: Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, Medical Faculty, 50937 Cologne, Germany
Michaela Thoenes: Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, Medical Faculty, 50937 Cologne, Germany
Alfredo Ramirez: Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, Medical Faculty, 50937 Cologne, Germany; Department of Neurodegeneration and Geriatric Psychiatry, University of Bonn, 53127 Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
Klaus Flissbach: Department of Neurodegeneration and Geriatric Psychiatry, University of Bonn, 53127 Bonn, Germany
Clara Grezella: Institut e of Reconstructive Neurobiology, Life & Brain Center, University of Bonn Medical Faculty, and University Hospital Bonn, Bonn 53127, Germany
Oliver Brüstle: Institut e of Reconstructive Neurobiology, Life & Brain Center, University of Bonn Medical Faculty, and University Hospital Bonn, Bonn 53127, Germany
Michael Peitz: Institut e of Reconstructive Neurobiology, Life & Brain Center, University of Bonn Medical Faculty, and University Hospital Bonn, Bonn 53127, Germany
Andreas Ebneth: Janssen Research & Development, Neuroscience Therapeutic Area (Johnson & Johnson), Turnhoutseweg 30, 2340 Beerse, Belgium; Cell Programming Core Facility, University of Bonn Medical Faculty, Bonn, Germany
Alfredo Cabrera-Socorro: Janssen Research & Development, Neuroscience Therapeutic Area (Johnson & Johnson), Turnhoutseweg 30, 2340 Beerse, Belgium; Corresponding author.

Journal volume & issue: Vol. 52
p. 102180

Abstract

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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).

Published in Stem Cell Research

ISSN: 1873-5061 (Print); 1876-7753 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: https://www.journals.elsevier.com/stem-cell-research

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