| Literature DB >> 28238547 |
Ira Espuny-Camacho1, Amaia M Arranz2, Mark Fiers1, An Snellinx1, Kunie Ando3, Sebastian Munck4, Jerome Bonnefont5, Laurie Lambot6, Nikky Corthout4, Lorna Omodho1, Elke Vanden Eynden1, Enrico Radaelli1, Ina Tesseur1, Selina Wray7, Andreas Ebneth8, John Hardy7, Karelle Leroy3, Jean-Pierre Brion3, Pierre Vanderhaeghen9, Bart De Strooper10.
Abstract
Human pluripotent stem cells (PSCs) provide a unique entry to study species-specific aspects of human disorders such as Alzheimer's disease (AD). However, in vitro culture of neurons deprives them of their natural environment. Here we transplanted human PSC-derived cortical neuronal precursors into the brain of a murine AD model. Human neurons differentiate and integrate into the brain, express 3R/4R Tau splice forms, show abnormal phosphorylation and conformational Tau changes, and undergo neurodegeneration. Remarkably, cell death was dissociated from tangle formation in this natural 3D model of AD. Using genome-wide expression analysis, we observed upregulation of genes involved in myelination and downregulation of genes related to memory and cognition, synaptic transmission, and neuron projection. This novel chimeric model for AD displays human-specific pathological features and allows the analysis of different genetic backgrounds and mutations during the course of the disease.Entities:
Keywords: Alzheimer’s disease; cell death; chimeric mouse; dystrophic neurites; expression analysis; human neurons; modeling; neurodegeneration; pluripotent stem cells
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Year: 2017 PMID： 28238547 DOI： 10.1016/j.neuron.2017.02.001
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 17.173