Your browser doesn't support javascript.
loading
The Impact of APP on Alzheimer-like Pathogenesis and Gene Expression in Down Syndrome iPSC-Derived Neurons.
Ovchinnikov, Dmitry A; Korn, Othmar; Virshup, Isaac; Wells, Christine A; Wolvetang, Ernst J.
Afiliación
  • Ovchinnikov DA; Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, QLD 4072, Australia.
  • Korn O; Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, QLD 4072, Australia.
  • Virshup I; Centre for Stem Cell Systems, MDHS, University of Melbourne, Melbourne, VIC 3010, Australia.
  • Wells CA; Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, QLD 4072, Australia; Centre for Stem Cell Systems, MDHS, University of Melbourne, Melbourne, VIC 3010, Australia.
  • Wolvetang EJ; Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, QLD 4072, Australia. Electronic address: e.wolvetang@uq.edu.au.
Stem Cell Reports ; 11(1): 32-42, 2018 07 10.
Article en En | MEDLINE | ID: mdl-29861166
Early-onset Alzheimer disease (AD)-like pathology in Down syndrome is commonly attributed to an increased dosage of the amyloid precursor protein (APP) gene. To test this in an isogenic human model, we deleted the supernumerary copy of the APP gene in trisomic Down syndrome induced pluripotent stem cells or upregulated APP expression in euploid human pluripotent stem cells using CRISPRa. Cortical neuronal differentiation shows that an increased APP gene dosage is responsible for increased ß-amyloid production, altered Aß42/40 ratio, and deposition of the pyroglutamate (E3)-containing amyloid aggregates, but not for several tau-related AD phenotypes or increased apoptosis. Transcriptome comparisons demonstrate that APP has a widespread and temporally modulated impact on neuronal gene expression. Collectively, these data reveal an important role for APP in the amyloidogenic aspects of AD but challenge the idea that increased APP levels are solely responsible for increasing specific phosphorylated forms of tau or enhanced neuronal cell death in Down syndrome-associated AD pathogenesis.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Expresión Génica / Precursor de Proteína beta-Amiloide / Síndrome de Down / Células Madre Pluripotentes Inducidas / Enfermedad de Alzheimer / Neuronas Tipo de estudio: Etiology_studies Límite: Humans Idioma: En Revista: Stem Cell Reports Año: 2018 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Expresión Génica / Precursor de Proteína beta-Amiloide / Síndrome de Down / Células Madre Pluripotentes Inducidas / Enfermedad de Alzheimer / Neuronas Tipo de estudio: Etiology_studies Límite: Humans Idioma: En Revista: Stem Cell Reports Año: 2018 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos