title: Increased susceptibility to Aβ toxicity in neuronal cultures derived from familial Alzheimer's disease (PSEN1-A246E) induced pluripotent stem cells.
abstract: Alzheimer's disease (AD) is the most common cause of late-life dementia and represents one of the leading causes of death worldwide. The generation of induced pluripotent stem cells (iPSC) has facilitated the production and differentiation of stem cells from patients somatic cells, offering new opportunities to model AD and other diseases in vitro. In this study, we generated iPSCs from skin fibroblasts obtained from a healthy individual, as well as sporadic (sAD) and familial AD (fAD, PSEN1-A246E mutation) patients. iPSC lines were differentiated into neuronal precursors (iPSC-NPCs) and neurons that were subjected to amyloid beta (Aβ) toxicity assays. We found that neurons derived from the fAD patient have a higher susceptibility to Aβ1-42 oligomers compared with neurons coming from healthy and sAD individuals. Our findings suggest that neurons from patients with PSEN1-A246E mutation have intrinsic properties that make them more susceptible to the toxic effects of Aβ1-42 oligomers in the AD brain.
authors.affiliation: Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, TX 77030, USA; Universidad de los Andes, Facultad de Medicina, Av. San Carlos de Apoquindo 2200, Las Condes, Santiago, Chile.
authors.forename: Enrique
authors.initials: E
authors.lastname: Armijo
authors.affiliation: Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, TX 77030, USA.
authors.forename: Cesar
authors.initials: C
authors.lastname: Gonzalez
authors.affiliation: Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, TX 77030, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shahnawaz
authors.affiliation: Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, TX 77030, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Flores
authors.affiliation: Center for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Davis
authors.affiliation: Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, TX 77030, USA; Universidad de los Andes, Facultad de Medicina, Av. San Carlos de Apoquindo 2200, Las Condes, Santiago, Chile. Electronic address: Claudio.Soto@uth.tmc.edu.
authors.forename: Claudio
authors.initials: C
authors.lastname: Soto
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004198:Disease Susceptibility / Q000139:chemically induced; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000166:cytology / Q000187:drug effects*
chemical_list: D016229:Amyloid beta-Peptides
keywords: Alzheimer’s disease; Amyloid-beta; Induced pluripotent stem cells; Neurotoxicity