{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:35:55Z","timestamp":1792100155642,"version":"4.4.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T00:00:00Z","timestamp":1591920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"DOI":"10.3389\/fncel.2020.00151","type":"journal-article","created":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T04:26:37Z","timestamp":1591935997000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":44,"title":["A Three-Dimensional Alzheimer\u2019s Disease Cell Culture Model Using iPSC-Derived Neurons Carrying A246E Mutation in PSEN1"],"prefix":"10.3389","volume":"14","author":[{"given":"Mercedes A.","family":"Hern\u00e1ndez-Sapi\u00e9ns","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin E.","family":"Reza-Zald\u00edvar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo R.","family":"Cevallos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana L.","family":"M\u00e1rquez-Aguirre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karlen","family":"Gazarian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro A.","family":"Canales-Aguirre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,6,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1016\/j.arcmed.2012.10.017","article-title":"Genetics of Alzheimer\u2019s disease","volume":"43","author":"Alonso Vilatela","year":"2012","journal-title":"Arch. Med. Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2029","DOI":"10.1038\/nprot.2012.130","article-title":"Passaging and colony expansion of human pluripotent stem cells by enzyme-free dissociation in chemically defined culture conditions","volume":"7","author":"Beers","year":"2012","journal-title":"Nat. Protoc."},{"key":"B3","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1016\/j.jalz.2016.01.012","article-title":"Molecular genetics of early-onset alzheimer\u2019s disease revisited","volume":"12","author":"Cacace","year":"2016","journal-title":"Alzheimers Dement."},{"key":"B4","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1002\/stem.2788","article-title":"Wnt\/\u03b2-catenin\/TCF pathway is a phase-dependent promoter of colony formation and mesendodermal differentiation during human somatic cell reprogramming","volume":"36","author":"Cevallos","year":"2018","journal-title":"Stem Cells"},{"key":"B5","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1038\/nbt.1529","article-title":"Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling","volume":"27","author":"Chambers","year":"2009","journal-title":"Nat. Biotechnol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"102","DOI":"10.17925\/USN.2015.11.02.102","article-title":"Recapitulating amyloid \u03b2 and tau pathology in human neural cell culture models: clinical implications","volume":"11","author":"Choi","year":"2015","journal-title":"US Neurol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1038\/nature13800","article-title":"A three-dimensional human neural cell culture model of Alzheimer\u2019s disease","volume":"515","author":"Choi","year":"2014","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s13024-016-0139-7","article-title":"3D culture models of Alzheimer\u2019s disease: a road map to a \u201ccure-in-a-dish\u201d","volume":"11","author":"Choi","year":"2016","journal-title":"Mol. Neurodegener."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1002\/bies.201500063","article-title":"Alzheimer\u2019s in 3D culture: challenges and perspectives","volume":"37","author":"D\u2019Avanzo","year":"2015","journal-title":"Bioessays"},{"key":"B10","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1097\/00002093-198802030-00015","article-title":"Alzheimer\u2019s in a dish\u2014induced pluripotent stem cell-based disease modeling","volume":"8","author":"de Leeuw","year":"2019","journal-title":"Transl. Neurodegener."},{"key":"B11","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1177\/1087057117696795","article-title":"Three-dimensional cell cultures in drug discovery and development","volume":"22","author":"Fang","year":"2017","journal-title":"SLAS Discov."},{"key":"B12","doi-asserted-by":"publisher","first-page":"015002","DOI":"10.1088\/1748-6041\/6\/1\/015002","article-title":"Fabrication and optimization of alginate hydrogel constructs for use in 3D neural cell culture","volume":"6","author":"Frampton","year":"2011","journal-title":"Biomed. Mater."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2363","DOI":"10.1038\/s41380-018-0229-8","article-title":"Modeling amyloid \u03b2 and tau pathology in human cerebral organoids","volume":"23","author":"Gonzalez","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"B14","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1146\/annurev-med-042915-103753","article-title":"Update on Alzheimer\u2019s disease therapy and prevention strategies","volume":"68","author":"Graham","year":"2017","journal-title":"Annu. Rev. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"5140","DOI":"10.1002\/adfm.201300435","article-title":"Silk hydrogels as soft substrates for neural tissue engineering","volume":"23","author":"Hopkins","year":"2013","journal-title":"Adv. Funct. Mater."},{"key":"B16","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s12864-015-1262-5","article-title":"Induced pluripotent stem cell-derived neuronal cells from a sporadic Alzheimer\u2019s disease donor as a model for investigating AD-associated gene regulatory networks","volume":"16","author":"Hossini","year":"2015","journal-title":"BMC Genomics"},{"key":"B17","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/nature10821","article-title":"Probing sporadic and familial Alzheimer\u2019s disease using induced pluripotent stem cells","volume":"482","author":"Israel","year":"2012","journal-title":"Nature"},{"key":"B18","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1073\/pnas.1619574114","article-title":"Presenilin-1 mutations and Alzheimer\u2019s disease","volume":"114","author":"Kelleher","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"B19","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1038\/nprot.2015.065","article-title":"A 3D human neural cell culture system for modeling Alzheimer\u2019s disease","volume":"10","author":"Kim","year":"2015","journal-title":"Nat. Protoc."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e1002270","DOI":"10.1371\/journal.pmed.1002270","article-title":"APP, PSEN1 and PSEN2 mutations in early-onset alzheimer disease: a genetic screening study of familial and sporadic cases","volume":"14","author":"Lanoisel\u00e9e","year":"2017","journal-title":"PLoS Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1730","DOI":"10.1523\/JNEUROSCI.2735-15.2016","article-title":"Single-cell detection of secreted A\u03b2 and sAPP\u03b1 from human IPSC-derived neurons and astrocytes","volume":"36","author":"Liao","year":"2016","journal-title":"J. Neurosci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1002\/cphy.c180025","article-title":"Studying human neurological disorders using induced pluripotent stem cells: from 2D monolayer to 3D organoid and blood brain barrier models","volume":"9","author":"Logan","year":"2019","journal-title":"Compr. Physiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2996","DOI":"10.1089\/scd.2013.0511","article-title":"Induced pluripotent stem cells from familial Alzheimer\u2019s disease patients differentiate into mature neurons with amyloidogenic properties","volume":"23","author":"Mahairaki","year":"2014","journal-title":"Stem Cells Dev."},{"key":"B24","doi-asserted-by":"publisher","first-page":"15056","DOI":"10.1038\/nrdp.2015.56","article-title":"Alzheimer\u2019s disease","volume":"1","author":"Masters","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"B25","doi-asserted-by":"publisher","first-page":"239","DOI":"10.4252\/wjsc.v6.i2.239","article-title":"Familial Alzheimer\u2019s disease modelling using induced pluripotent stem cell technology","volume":"6","author":"Mohamet","year":"2014","journal-title":"World J. Stem Cells"},{"key":"B26","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.scr.2018.08.006","article-title":"Generation and characterization of human induced pluripotent stem cell lines from a familial Alzheimer\u2019s disease PSEN1 A246E patient and a non-demented family member bearing wild-type PSEN1","volume":"31","author":"Mu\u00f1oz","year":"2018","journal-title":"Stem Cell Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.3415","article-title":"Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture","volume":"12","author":"Pa\u015fca","year":"2015","journal-title":"Nat. Methods"},{"key":"B28","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1038\/s41380-019-0468-3","article-title":"Modeling Alzheimer\u2019s disease with iPSC-derived brain cells","volume":"25","author":"Penney","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"B29","doi-asserted-by":"publisher","first-page":"3038","DOI":"10.3390\/ijms13033038","article-title":"Unraveling the early events of amyloid-\u03b2 protein (A\u03b2) aggregation: techniques for the determination of A\u03b2 aggregate size","volume":"13","author":"Pryor","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1038\/nbt.3777","article-title":"Combined small-molecule inhibition accelerates the derivation of functional cortical neurons from human pluripotent stem cells","volume":"35","author":"Qi","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"e0161969","DOI":"10.1371\/journal.pone.0161969","article-title":"Self-organizing 3D human neural tissue derived from induced pluripotent stem cells recapitulate Alzheimer\u2019s disease phenotypes","volume":"11","author":"Raja","year":"2016","journal-title":"PLoS One"},{"key":"B32","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1002\/jcp.24683","article-title":"3D cell culture systems: advantages and applications","volume":"230","author":"Ravi","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1515\/revneuro-2017-0063","article-title":"Amyloid toxicity in Alzheimer\u2019s disease","volume":"29","author":"Reiss","year":"2018","journal-title":"Rev. Neurosci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.4103\/1673-5374.255978","article-title":"Mesenchymal stem cell-derived exosomes promote neurogenesis and cognitive function recovery in a mouse model of Alzheimer\u2019s disease","volume":"14","author":"Reza-Zaldivar","year":"2019","journal-title":"Neural Regen. Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"99","DOI":"10.2217\/bmm.09.92","article-title":"Correlating familial Alzheimer\u2019s disease gene mutations with clinical phenotype","volume":"4","author":"Ryan","year":"2010","journal-title":"Biomark. Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1159\/000464422","article-title":"Molecular pathogenesis of Alzheimer\u2019s disease: an update","volume":"24","author":"Sanabria-Castro","year":"2017","journal-title":"Ann. Neurosci."},{"key":"B37","doi-asserted-by":"publisher","first-page":"77","DOI":"10.3389\/fphar.2013.00077","article-title":"Modeling Alzheimer\u2019s disease: from past to future","volume":"4","author":"Saraceno","year":"2013","journal-title":"Front. Pharmacol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1836","DOI":"10.1038\/nprot.2012.116","article-title":"Directed differentiation of human pluripotent stem cells to cerebral cortex neurons and neural networks","volume":"7","author":"Shi","year":"2012","journal-title":"Nat. Protoc."},{"key":"B39","doi-asserted-by":"publisher","first-page":"e84547","DOI":"10.1371\/journal.pone.0084547","article-title":"Characterization and molecular profiling of PSEN1 familial Alzheimer\u2019s disease iPSC-derived neural progenitors","volume":"9","author":"Sproul","year":"2014","journal-title":"PLoS One"},{"key":"B40","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1126\/science.282.5391.1145","article-title":"Embryonic stem cell lines derived from human blastocysts","volume":"282","author":"Thomson","year":"1998","journal-title":"Science"},{"key":"B42","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1001\/archneurol.2011.31","article-title":"Cognitive decline in prodromal alzheimer disease and mild cognitive impairment","volume":"68","author":"Wilson","year":"2011","journal-title":"JAMA Neurol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"4530","DOI":"10.1093\/hmg\/ddr394","article-title":"Modeling familial Alzheimer\u2019s disease with induced pluripotent stem cells","volume":"20","author":"Yagi","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1016\/j.biomaterials.2013.11.028","article-title":"A 3D Alzheimer\u2019s disease culture model and the induction of P21-activated kinase mediated sensing in iPSC derived neurons","volume":"35","author":"Zhang","year":"2014","journal-title":"Biomaterials"}],"container-title":["Frontiers in Cellular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fncel.2020.00151\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T04:26:39Z","timestamp":1591935999000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fncel.2020.00151\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,12]]},"references-count":44,"alternative-id":["10.3389\/fncel.2020.00151"],"URL":"https:\/\/doi.org\/10.3389\/fncel.2020.00151","relation":{},"ISSN":["1662-5102"],"issn-type":[{"value":"1662-5102","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,12]]},"article-number":"151"}}