{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T07:05:36Z","timestamp":1792047936494,"version":"4.4.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"7526","license":[{"start":{"date-parts":[[2014,10,12]],"date-time":"2014-10-12T00:00:00Z","timestamp":1413072000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2014,10,12]],"date-time":"2014-10-12T00:00:00Z","timestamp":1413072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2014,11,13]]},"DOI":"10.1038\/nature13800","type":"journal-article","created":{"date-parts":[[2014,10,10]],"date-time":"2014-10-10T10:09:50Z","timestamp":1412935790000},"page":"274-278","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1129,"title":["A three-dimensional human neural cell culture model of Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"515","author":[{"given":"Se Hoon","family":"Choi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Hye","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Hebisch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Sliwinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seungkyu","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"D\u2019Avanzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hechao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basavaraj","family":"Hooli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Asselin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Muffat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin B.","family":"Klee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Wainger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Peitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dora M.","family":"Kovacs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifford J.","family":"Woolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven L.","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolph E.","family":"Tanzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doo Yeon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,10,12]]},"reference":[{"key":"BFnature13800_CR1","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.cell.2005.02.008","volume":"120","author":"RE Tanzi","year":"2005","unstructured":"Tanzi, R. E. & Bertram, L. Twenty years of the Alzheimer\u2019s disease amyloid hypothesis: a genetic perspective. Cell 120, 545\u2013555 (2005)","journal-title":"Cell"},{"key":"BFnature13800_CR2","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1126\/science.1072994","volume":"297","author":"J Hardy","year":"2002","unstructured":"Hardy, J. & Selkoe, D. J. The amyloid hypothesis of Alzheimer\u2019s disease: progress and problems on the road to therapeutics. Science 297, 353\u2013356 (2002)","journal-title":"Science"},{"key":"BFnature13800_CR3","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1126\/science.1074069","volume":"298","author":"D Selkoe","year":"2002","unstructured":"Selkoe, D. Alzheimer\u2019s disease is a synaptic failure. Science 298, 789\u2013791 (2002)","journal-title":"Science"},{"key":"BFnature13800_CR4","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1042\/bss0670195","volume":"67","author":"K Duff","year":"2001","unstructured":"Duff, K. Transgenic mouse models of Alzheimer\u2019s disease: phenotype and mechanisms of pathogenesis. Biochem. Soc. Symp. 67, 195\u2013202 (2001)","journal-title":"Biochem. Soc. Symp."},{"key":"BFnature13800_CR5","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1007\/978-1-60761-744-0_13","volume":"670","author":"J Chin","year":"2011","unstructured":"Chin, J. Selecting a mouse model of Alzheimer\u2019s disease. Methods Mol. Biol. 670, 169\u2013189 (2011)","journal-title":"Methods Mol. Biol."},{"key":"BFnature13800_CR6","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.stem.2012.02.011","volume":"10","author":"SH Choi","year":"2012","unstructured":"Choi, S. H. & Tanzi, R. E. iPSCs to the rescue in Alzheimer\u2019s research. Cell Stem Cell 10, 235\u2013236 (2012)","journal-title":"Cell Stem Cell"},{"key":"BFnature13800_CR7","doi-asserted-by":"publisher","first-page":"4530","DOI":"10.1093\/hmg\/ddr394","volume":"20","author":"T Yagi","year":"2011","unstructured":"Yagi, T. et al. Modeling familial Alzheimer\u2019s disease with induced pluripotent stem cells. Hum. Mol. Genet. 20, 4530\u20134539 (2011)","journal-title":"Hum. Mol. Genet."},{"key":"BFnature13800_CR8","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/nature10821","volume":"482","author":"MA Israel","year":"2012","unstructured":"Israel, M. A. et al. Probing sporadic and familial Alzheimer\u2019s disease using induced pluripotent stem cells. Nature 482, 216\u2013220 (2012)","journal-title":"Nature"},{"key":"BFnature13800_CR9","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.stem.2013.01.009","volume":"12","author":"T Kondo","year":"2013","unstructured":"Kondo, T. et al. Modeling Alzheimer\u2019s disease with iPSCs reveals stress phenotypes associated with intracellular A\u03b2 and differential drug responsiveness. Cell Stem Cell 12, 487\u2013496 (2013)","journal-title":"Cell Stem Cell"},{"key":"BFnature13800_CR10","doi-asserted-by":"publisher","first-page":"3523","DOI":"10.1093\/hmg\/ddu064","volume":"23","author":"CR Muratore","year":"2014","unstructured":"Muratore, C. R. et al. The familial Alzheimer\u2019s disease APPV717I mutation alters APP processing and Tau expression in iPSC-derived neurons. Hum. Mol. Genet. 23, 3523\u20133536 (2014)","journal-title":"Hum. Mol. Genet."},{"key":"BFnature13800_CR11","doi-asserted-by":"publisher","first-page":"e84547","DOI":"10.1371\/journal.pone.0084547","volume":"9","author":"AA Sproul","year":"2014","unstructured":"Sproul, A. A. et al. Characterization and molecular profiling of PSEN1 familial Alzheimer\u2019s disease iPSC-derived neural progenitors. PLoS ONE 9, e84547 (2014)","journal-title":"PLoS ONE"},{"key":"BFnature13800_CR12","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/1471-2202-8-36","volume":"8","author":"R Donato","year":"2007","unstructured":"Donato, R. et al. Differential development of neuronal physiological responsiveness in two human neural stem cell lines. BMC Neurosci. 8, 36 (2007)","journal-title":"BMC Neurosci."},{"key":"BFnature13800_CR13","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1097\/WNR.0b013e32832fbf49","volume":"20","author":"PJ Morgan","year":"2009","unstructured":"Morgan, P. J. et al. Protection of neurons derived from human neural progenitor cells by veratridine. Neuroreport 20, 1225\u20131229 (2009)","journal-title":"Neuroreport"},{"key":"BFnature13800_CR14","doi-asserted-by":"publisher","first-page":"515","DOI":"10.2478\/s11658-011-0021-0","volume":"16","author":"O Mazemondet","year":"2011","unstructured":"Mazemondet, O. et al. Quantitative and kinetic profile of Wnt\/\u03b2-catenin signaling components during human neural progenitor cell differentiation. Cell. Mol. Biol. Lett. 16, 515\u2013538 (2011)","journal-title":"Cell. Mol. Biol. Lett."},{"key":"BFnature13800_CR15","doi-asserted-by":"publisher","first-page":"e48824","DOI":"10.1371\/journal.pone.0048824","volume":"7","author":"H Li","year":"2012","unstructured":"Li, H., Wijekoon, A. & Leipzig, N. D. 3D differentiation of neural stem cells in macroporous photopolymerizable hydrogel scaffolds. PLoS ONE 7, e48824 (2012)","journal-title":"PLoS ONE"},{"key":"BFnature13800_CR16","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/nature12517","volume":"501","author":"MA Lancaster","year":"2013","unstructured":"Lancaster, M. A. et al. Cerebral organoids model human brain development and microcephaly. Nature 501, 373\u2013379 (2013)","journal-title":"Nature"},{"key":"BFnature13800_CR17","doi-asserted-by":"publisher","unstructured":"Tang-Schomer, M. D. et al. Bioengineered functional brain-like cortical tissue. Proc. Natl Acad. Sci. USA \n                    http:\/\/dx.doi.org\/10.1073\/pnas.1324214111\n                    \n                   (August 11, 2014)","DOI":"10.1073\/pnas.1324214111"},{"key":"BFnature13800_CR18","unstructured":"Higuchi, M., Trojanowski, J. Q. & Lee, V. M.-Y. Tau protein and tauopathy. Neuropsychopharmacology: The Fifth Generation of Progress (eds Davis, K. L., Charney, D., Coyle, J. T. & Nemeroff, C. ) 1339\u20131354 (Lippincott, Williams & Wilkins, 2002)"},{"key":"BFnature13800_CR19","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1021\/bi401537v","volume":"53","author":"SL Wagner","year":"2014","unstructured":"Wagner, S. L. et al. Soluble \u03b3-secretase modulators selectively inhibit the production of the 42-amino acid amyloid \u03b2 peptide variant and augment the production of multiple carboxy-truncated amyloid \u03b2 species. Biochemistry 53, 702\u2013713 (2014)","journal-title":"Biochemistry"},{"key":"BFnature13800_CR20","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/S0025-7125(02)00002-0","volume":"86","author":"JQ Trojanowski","year":"2002","unstructured":"Trojanowski, J. Q. & Lee, V. M.-Y. The role of tau in Alzheimer\u2019s disease. Med. Clin. North Am. 86, 615\u2013627 (2002)","journal-title":"Med. Clin. North Am."},{"key":"BFnature13800_CR21","first-page":"241","volume":"137","author":"P Cras","year":"1990","unstructured":"Cras, P. et al. Neuronal and microglial involvement in \u03b2-amyloid protein deposition in Alzheimer\u2019s disease. Am. J. Pathol. 137, 241\u2013246 (1990)","journal-title":"Am. J. Pathol."},{"key":"BFnature13800_CR22","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/S0076-6879(83)03027-X","volume":"103","author":"JV Nadler","year":"1983","unstructured":"Nadler, J. V. & Evenson, D. A. Use of excitatory amino acids to make axon-sparing lesions of hypothalamus. Methods Enzymol. 103, 393\u2013400 (1983)","journal-title":"Methods Enzymol."},{"key":"BFnature13800_CR23","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.bmcl.2003.10.062","volume":"14","author":"C Kunick","year":"2004","unstructured":"Kunick, C., Lauenroth, K., Leost, M., Meijer, L. & Lemcke, T. 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3\u03b2. Bioorg. Med. Chem. Lett. 14, 413\u2013416 (2004)","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"BFnature13800_CR24","doi-asserted-by":"publisher","first-page":"e39329","DOI":"10.1371\/journal.pone.0039329","volume":"7","author":"LA Kirby","year":"2012","unstructured":"Kirby, L. A. et al. Glycogen synthase kinase 3 (GSK3) inhibitor, SB-216763, promotes pluripotency in mouse embryonic stem cells. PLoS ONE 7, e39329 (2012)","journal-title":"PLoS ONE"},{"key":"BFnature13800_CR25","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1038\/nature01640","volume":"423","author":"CJ Phiel","year":"2003","unstructured":"Phiel, C. J., Wilson, C. A., Lee, V. M.-Y. & Klein, P. S. GSK-3\u03b1 regulates production of Alzheimer\u2019s disease amyloid-\u03b2 peptides. Nature 423, 435\u2013439 (2003)","journal-title":"Nature"},{"key":"BFnature13800_CR26","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1038\/nature01640","volume":"423","author":"T Jaworski","year":"2003","unstructured":"Jaworski, T. et al. GSK-3\u03b1\/\u03b2 kinases and amyloid production in vivo. Nature 423, 435\u2013439 (2003)","journal-title":"Nature"},{"key":"BFnature13800_CR27","doi-asserted-by":"publisher","first-page":"6245","DOI":"10.1523\/JNEUROSCI.3672-12.2013","volume":"33","author":"RM Cohen","year":"2013","unstructured":"Cohen, R. M. et al. A transgenic Alzheimer rat with plaques, tau pathology, behavioral impairment, oligomeric A\u03b2, and frank neuronal loss. J. Neurosci. 33, 6245\u20136256 (2013)","journal-title":"J. Neurosci."},{"key":"BFnature13800_CR28","doi-asserted-by":"publisher","first-page":"2595","DOI":"10.1096\/fj.08-122424","volume":"23","author":"E Planel","year":"2009","unstructured":"Planel, E. et al. Acceleration and persistence of neurofibrillary pathology in a mouse model of tauopathy following anesthesia. FASEB J. 23, 2595\u20132604 (2009)","journal-title":"FASEB J."},{"key":"BFnature13800_CR29","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1007\/978-1-61779-551-0_32","volume":"849","author":"C Julien","year":"2012","unstructured":"Julien, C., Bretteville, A. & Planel, E. Biochemical isolation of insoluble tau in transgenic mouse models of tauopathies. Methods Mol. Biol. 849, 473\u2013491 (2012)","journal-title":"Methods Mol. Biol."},{"key":"BFnature13800_CR30","doi-asserted-by":"publisher","first-page":"e13947","DOI":"10.1371\/journal.pone.0013947","volume":"5","author":"M Iovino","year":"2010","unstructured":"Iovino, M., Patani, R., Watts, C., Chandran, S. & Spillantini, M. G. Human stem cell-derived neurons: a system to study human tau function and dysfunction. PLoS ONE 5, e13947 (2010)","journal-title":"PLoS ONE"}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nature13800.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature13800","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature13800.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T14:25:18Z","timestamp":1684419918000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nature13800"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,12]]},"references-count":30,"journal-issue":{"issue":"7526","published-print":{"date-parts":[[2014,11,13]]}},"alternative-id":["BFnature13800"],"URL":"https:\/\/doi.org\/10.1038\/nature13800","relation":{},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,12]]},"assertion":[{"value":"28 January 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 August 2014","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 October 2014","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}