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dc.contributor.authorOrtiz Virumbrales, Maitane
dc.contributor.authorMoreno, César L.
dc.contributor.authorKruglikov, Ilya
dc.contributor.authorMarazuela, Paula
dc.contributor.authorSproul, Andrew
dc.contributor.authorJacob, Samson
dc.contributor.authorZimmer, Matthew
dc.contributor.authorPaull, Daniel
dc.contributor.authorZhang, Bin
dc.contributor.authorSchadt, Eric E.
dc.contributor.authorEhrlich, Michelle E.
dc.contributor.authorTanzi, Rudolph E.
dc.contributor.authorArancio, Ottavio
dc.contributor.authorNoggle, Scott
dc.contributor.authorGandy, Sam
dc.date.accessioned2020-01-15T11:45:54Z
dc.date.available2020-01-15T11:45:54Z
dc.date.issued2017
dc.identifier.issn2051-5960spa
dc.identifier.urihttp://hdl.handle.net/10641/1790
dc.description.abstractBasal forebrain cholinergic neurons (BFCNs) are believed to be one of the first cell types to be affected in all forms of AD, and their dysfunction is clinically correlated with impaired short-term memory formation and retrieval. We present an optimized in vitro protocol to generate human BFCNs from iPSCs, using cell lines from presenilin 2 (PSEN2) mutation carriers and controls. As expected, cell lines harboring the PSEN2N141I mutation displayed an increase in the Aβ42/40 in iPSC-derived BFCNs. Neurons derived from PSEN2N141I lines generated fewer maximum number of spikes in response to a square depolarizing current injection. The height of the first action potential at rheobase current injection was also significantly decreased in PSEN2N141I BFCNs. CRISPR/Cas9 correction of the PSEN2 point mutation abolished the electrophysiological deficit, restoring both the maximal number of spikes and spike height to the levels recorded in controls. Increased Aβ42/40 was also normalized following CRISPR/Casmediated correction of the PSEN2N141I mutation. The genome editing data confirms the robust consistency of mutation-related changes in Aβ42/40 ratio while also showing a PSEN2-mutation-related alteration in electrophysiology.spa
dc.language.isoengspa
dc.publisherActa Neuropathologica Communicationsspa
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 España*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/*
dc.subjectAlzheimer’s diseasespa
dc.subjectElectrophysiologyspa
dc.subjectBasal forebrainspa
dc.subjectCholinergicspa
dc.subjectPresenilinspa
dc.titleCRISPR/Cas9-Correctable mutation-related molecular and physiological phenotypes in iPSC-derived Alzheimer’s PSEN2N141I neurons.spa
dc.typearticlespa
dc.description.versionpost-printspa
dc.rights.accessRightsopenAccessspa
dc.description.extent6813 KBspa
dc.identifier.doi10.1186/s40478-017-0475-zspa
dc.relation.publisherversionhttps://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-017-0475-zspa


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Except where otherwise noted, this item's license is described as Atribución-NoComercial-SinDerivadas 3.0 España