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- W2892315788 abstract "Abstract We describe construction and phenotypic analysis of a human embryonic stem cell model of progressive Aβ-dependent neurodegeneration (ND) with potential relevance to Alzheimer’s disease (AD). We modified one allele of the normal APP locus to directly express a secretory form of Aβ40 or Aβ42, eliminating the need for amyloidogenic APP proteolysis. Following neuronal differentiation edited cell lines specifically accumulate aggregated/oligomeric Aβ, exhibit a synaptic deficit and have an abnormal accumulation of endolysosomal vesicles. Edited cultures progress to a stage of overt ND. All phenotypes appear at earlier culture times for Aβ42 relative to Aβ40. Whole transcriptome RNA-Seq analysis identified 23 up and 70 down regulated genes (DEGs) with similar directional fold change but larger absolute values in the Aβ42 samples suggesting common underlying pathogenic mechanisms. Pathway/annotation analysis suggested that down regulation of extracellular matrix and cilia functions are significantly overrepresented. This cellular model could be useful for uncovering mechanisms directly linking Aβ to neuronal death and as a tool to screen for new therapeutic agents that slow or prevent human ND." @default.
- W2892315788 created "2018-09-27" @default.
- W2892315788 creator A5006945247 @default.
- W2892315788 creator A5017980532 @default.
- W2892315788 creator A5034259576 @default.
- W2892315788 creator A5058170576 @default.
- W2892315788 creator A5068242288 @default.
- W2892315788 creator A5081928612 @default.
- W2892315788 date "2018-09-17" @default.
- W2892315788 modified "2023-09-27" @default.
- W2892315788 title "A human embryonic stem cell model of Aβ-dependent chronic progressive neurodegeneration" @default.
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