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dc.contributor.authorOvchinnikov, DA
dc.contributor.authorKorn, O
dc.contributor.authorVirshup, I
dc.contributor.authorWells, CA
dc.contributor.authorWolvetang, EJ
dc.date.accessioned2020-12-17T04:11:04Z
dc.date.available2020-12-17T04:11:04Z
dc.date.issued2018-07-10
dc.identifierpii: S2213-6711(18)30221-2
dc.identifier.citationOvchinnikov, D. A., Korn, O., Virshup, I., Wells, C. A. & Wolvetang, E. J. (2018). The Impact of APP on Alzheimer-like Pathogenesis and Gene Expression in Down Syndrome iPSC-Derived Neurons. STEM CELL REPORTS, 11 (1), pp.32-42. https://doi.org/10.1016/j.stemcr.2018.05.004.
dc.identifier.issn2213-6711
dc.identifier.urihttp://hdl.handle.net/11343/255197
dc.description.abstractEarly-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 β-amyloid production, altered Aβ42/40 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.
dc.languageEnglish
dc.publisherCELL PRESS
dc.titleThe Impact of APP on Alzheimer-like Pathogenesis and Gene Expression in Down Syndrome iPSC-Derived Neurons
dc.typeJournal Article
dc.identifier.doi10.1016/j.stemcr.2018.05.004
melbourne.affiliation.departmentAnatomy and Neuroscience
melbourne.source.titleStem Cell Reports
melbourne.source.volume11
melbourne.source.issue1
melbourne.source.pages32-42
dc.rights.licenseCC BY
melbourne.elementsid1331722
melbourne.contributor.authorWells, Christine
melbourne.contributor.authorVirshup, Isaac
dc.identifier.eissn2213-6711
melbourne.accessrightsOpen Access


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