title: Neurons Derived from Induced Pluripotent Stem Cells of Patients with Down Syndrome Reproduce Early Stages of Alzheimer's Disease Type Pathology in vitro.
abstract: People with Down syndrome (DS) are at high risk of developing pathology similar to Alzheimer's disease (AD). Modeling of this pathology in vitro may be useful for studying this phenomenon. In this study, we analyzed three different cultures of neural cells carrying trisomy of chromosome 21, which were generated by directed differentiation from induced pluripotent stem cells (iPS cells). We report here that in vitro generated DS neural cells have abnormal metabolism of amyloid-β (Aβ) manifested by increased secretion and accumulation of Aβ granules of Aβ42 pathological isoform with upregulated expression of the APP gene. Additionally, we found increased expression levels of genes that are considered to be associated with AD (BACE2, RCAN1, ETS2, TMED10), as compared to healthy controls. Thus, the neural cells generated from induced pluripotent stem cells with DS reproduce initial cellular signs of AD-type pathology and can be useful tools for modeling and studying this variant of AD in vitro.
authors.affiliation: Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia.|Pirogov Russian National Research Medical University, Moscow, Russia.
authors.forename: Erdem B
authors.initials: EB
authors.lastname: Dashinimaev
authors.affiliation: Pirogov Russian National Research Medical University, Moscow, Russia.|Moscow Institute of Physics and Technology (State University), Dolgoprudny, Russia.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Artyuhov
authors.affiliation: Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Alexey P
authors.initials: AP
authors.lastname: Bolshakov
authors.affiliation: Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia.|Pirogov Russian National Research Medical University, Moscow, Russia.|Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Ekaterina A
authors.initials: EA
authors.lastname: Vorotelyak
authors.affiliation: Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia.|Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Vasiliev
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D015153:Blotting, Western; D004314:Down Syndrome / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000473:pathology; D007621:Karyotyping; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)
keywords: APP; Alzheimer’s disease; Aβ42; BACE2; Down syndrome; ETS2; IPSC; RCAN1; TMED10; amyloid-β