Journal article
The Impact of APP on Alzheimer-like Pathogenesis and Gene Expression in Down Syndrome iPSC-Derived Neurons
DA Ovchinnikov, O Korn, I Virshup, CA Wells, EJ Wolvetang
Stem Cell Reports | CELL PRESS | Published : 2018
Open access
Abstract
Wolvetang and colleagues used CRISPR/Cas9 technologies to manipulate the copy number and expression of the amyloid precursor protein (APP) gene in Down syndrome and corresponding euploid pluripotent stem cells. They demonstrate that APP modulates the expression of a surprisingly large cohort of genes and dictates Aβ42/40 ratio and pyroglutamate-E3 foci but does not affect hyperphosphorylated forms of tau associated with Alzheimer disease or neuronal cell death of in vitro generated cortical neurons.
Grants
Awarded by Australian Research Council
Funding Acknowledgements
We acknowledge funding from the Australian Research Council's Special Research Initiative "Stem Cells Australia" and the Australian National Health and Medical Research Council grant (NHMRC APP1062802). We thank Rowland Mosbergen, Sally Martin, and Tyrone Chen for technical assistance, Drs. R. Medeiros and P. Davis for providing the MC1 antibody, and all researchers who deposited plasmids in the Addgene repository. This work was performed in part at the University of Queensland node of the Australian National Fabrication Facility, a company established under the National Collaborative Research Infrastructure Strategy to provide nano- and micro-fabrication facilities for Australia's researchers.