{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:35:47Z","timestamp":1792154147956,"version":"4.4.0"},"reference-count":213,"publisher":"The Royal Society","issue":"9","license":[{"start":{"date-parts":[[2018,9,1]],"date-time":"2018-09-01T00:00:00Z","timestamp":1535760000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"funder":[{"DOI":"10.13039\/501100003448","name":"Hellenic General Secretariat for Research and Technology","doi-asserted-by":"crossref","award":["KRIPIS 2014-2020 \/ MIS 5002486"],"award-info":[{"award-number":["KRIPIS 2014-2020 \/ MIS 5002486"]}],"id":[{"id":"10.13039\/501100003448","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004343","name":"Stavros Niarchos Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004343","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Open Biol."],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:p>Synaptic dysfunction in CNS disorders is the outcome of perturbations in physiological synapse structure and function, and can be either the cause or the consequence in specific pathologies. Accumulating data in the field of neuropsychiatric disorders, including autism spectrum disorders, schizophrenia and bipolar disorder, point to a neurodevelopmental origin of these pathologies. Due to a relatively early onset of behavioural and cognitive symptoms, it is generally acknowledged that mental illness initiates at the synapse level. On the other hand, synaptic dysfunction has been considered as an endpoint incident in neurodegenerative diseases, such as Alzheimer's, Parkinson's and Huntington's, mainly due to the considerably later onset of clinical symptoms and progressive appearance of cognitive deficits. This dichotomy has recently been challenged, particularly since the discovery of cell reprogramming technologies and the generation of induced pluripotent stem cells from patient somatic cells. The creation of \u2018disease-in-a-dish\u2019 models for multiple CNS pathologies has revealed unexpected commonalities in the molecular and cellular mechanisms operating in both developmental and degenerative conditions, most of which meet at the synapse level. In this review we discuss synaptic dysfunction in prototype neurodevelopmental and neurodegenerative diseases, emphasizing overlapping features of synaptopathy that have been suggested by studies using induced pluripotent stem-cell-based systems. These valuable disease models have highlighted a potential neurodevelopmental component in classical neurodegenerative diseases that is worth pursuing and investigating further. Moving from demonstration of correlation to understanding mechanistic causality forms the basis for developing novel therapeutics.<\/jats:p>","DOI":"10.1098\/rsob.180138","type":"journal-article","created":{"date-parts":[[2018,9,5]],"date-time":"2018-09-05T07:17:16Z","timestamp":1536131836000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":206,"title":["Synaptic dysfunction in neurodegenerative and neurodevelopmental diseases: an overview of induced pluripotent stem-cell-based disease models"],"prefix":"10.1098","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6033-0261","authenticated-orcid":false,"given":"Era","family":"Taoufik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Kouroupi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ourania","family":"Zygogianni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Matsas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2018,9,5]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/8081758"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.019"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature25032"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-017-0498-x"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13713"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.06.012"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0248-4900(02)00016-3"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.31.060407.125646"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13702"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a005678"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a005694"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.R115.051482"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1252884"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.02.027"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2014.02.003"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1370"},{"key":"e_1_3_5_18_2","first-page":"420","article-title":"Axo-somatic and axo-dendritic synapses of the cerebral cortex: an electron microscope study","volume":"93","author":"Gray EG","year":"1959","unstructured":"Gray EG. 1959 Axo-somatic and axo-dendritic synapses of the cerebral cortex: an electron microscope study. J. Anat. 93, 420\u2013433.","journal-title":"J. Anat."},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01735373"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509527102"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2017.03.005"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.10.024"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.10.006"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2017.05.019"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2011.09.001"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2015.01.004"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2007.01.011"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2010.08.016"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2016.09.017"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/2643943"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.05.026"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3406"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(00)00200-8"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2017.03.008"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2015.02.002"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2017.01.015"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/6798712"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201709072"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2016.07.054"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-017-0077-5"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a009886"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2017.09.007"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1186\/1744-9081-5-11"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2016.245"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2016.46"},{"issue":"124","key":"e_1_3_5_46_2","first-page":"a29","article-title":"A human stem cell model of early Alzheimer's disease pathology in Down syndrome","volume":"4","author":"Shi Y","year":"2012","unstructured":"Shi Y, Kirwan P, Smith J, MacLean G, Orkin SH, Livesey FJ. 2012 A human stem cell model of early Alzheimer's disease pathology in Down syndrome. Sci. Transl. Med. 4(124r), a29.","journal-title":"Sci. Transl. Med."},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.05.029"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2013.04.008"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2014.01.009"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1529"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2014-0083"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/4190438"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.00237"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2017.56"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.3791\/54900"},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1504393112"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3507"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1186\/1756-6606-5-17"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.03.042"},{"key":"e_1_3_5_60_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.123851"},{"key":"e_1_3_5_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12354"},{"key":"e_1_3_5_62_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1823"},{"key":"e_1_3_5_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.12.013"},{"key":"e_1_3_5_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.12.018"},{"key":"e_1_3_5_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12929"},{"key":"e_1_3_5_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2015.05.004"},{"key":"e_1_3_5_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2014.22"},{"key":"e_1_3_5_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2013.11.006"},{"key":"e_1_3_5_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2011.01.013"},{"key":"e_1_3_5_70_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003985"},{"key":"e_1_3_5_71_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1617259114"},{"key":"e_1_3_5_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.05.022"},{"key":"e_1_3_5_73_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10821"},{"key":"e_1_3_5_74_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4532"},{"key":"e_1_3_5_75_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5430"},{"key":"e_1_3_5_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2017.06.012"},{"key":"e_1_3_5_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2008.10.001"},{"key":"e_1_3_5_78_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3415"},{"key":"e_1_3_5_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2016.07.005"},{"key":"e_1_3_5_80_2","doi-asserted-by":"publisher","DOI":"10.14573\/altex.1609122"},{"key":"e_1_3_5_81_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12517"},{"key":"e_1_3_5_82_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.06.034"},{"key":"e_1_3_5_83_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.04.032"},{"key":"e_1_3_5_84_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2017.07.014"},{"key":"e_1_3_5_85_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature22330"},{"key":"e_1_3_5_86_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0161969"},{"key":"e_1_3_5_87_2","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12396"},{"key":"e_1_3_5_88_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1715865115"},{"key":"e_1_3_5_89_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2017.107"},{"key":"e_1_3_5_90_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4214"},{"key":"e_1_3_5_91_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2016.12.007"},{"key":"e_1_3_5_92_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.45"},{"key":"e_1_3_5_93_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.10.016"},{"key":"e_1_3_5_94_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12618"},{"key":"e_1_3_5_95_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026203"},{"key":"e_1_3_5_96_2","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2014.0030"},{"key":"e_1_3_5_97_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-016-0194-6"},{"key":"e_1_3_5_98_2","first-page":"582","article-title":"Molecular analyses of neurogenic defects in a human pluripotent stem cell model of fragile X syndrome","volume":"140","author":"Boland MJ","year":"2017","unstructured":"Boland MJ et al. 2017 Molecular analyses of neurogenic defects in a human pluripotent stem cell model of fragile X syndrome. Brain 140, 582\u2013598.","journal-title":"Brain"},{"key":"e_1_3_5_99_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3307"},{"key":"e_1_3_5_100_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-014-0075-5"},{"key":"e_1_3_5_101_2","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2014.141"},{"key":"e_1_3_5_102_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09915"},{"key":"e_1_3_5_103_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13716"},{"key":"e_1_3_5_104_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2014.05.003"},{"key":"e_1_3_5_105_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.63.6.694"},{"key":"e_1_3_5_106_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aab3897"},{"key":"e_1_3_5_107_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2003.10.006"},{"key":"e_1_3_5_108_2","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(20010115)98:2<161::AID-AJMG1025>3.0.CO;2-B"},{"key":"e_1_3_5_109_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/10.10.981"},{"key":"e_1_3_5_110_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20337"},{"key":"e_1_3_5_111_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.08.045"},{"key":"e_1_3_5_112_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2009.05881.x"},{"key":"e_1_3_5_113_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-091212-153431"},{"key":"e_1_3_5_114_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2014.02.015"},{"key":"e_1_3_5_115_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13772"},{"key":"e_1_3_5_116_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2015.09.002"},{"key":"e_1_3_5_117_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1138-1"},{"key":"e_1_3_5_118_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.182"},{"key":"e_1_3_5_119_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2013.00085"},{"key":"e_1_3_5_120_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1146221"},{"key":"e_1_3_5_121_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2009.03.005"},{"key":"e_1_3_5_122_2","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2011.154"},{"key":"e_1_3_5_123_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13595"},{"key":"e_1_3_5_124_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2006.05.023"},{"key":"e_1_3_5_125_2","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbp079"},{"key":"e_1_3_5_126_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature16549"},{"key":"e_1_3_5_127_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2012.08.001"},{"key":"e_1_3_5_128_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07229"},{"key":"e_1_3_5_129_2","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12297"},{"key":"e_1_3_5_130_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2017.04.002"},{"key":"e_1_3_5_131_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.24"},{"key":"e_1_3_5_132_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1532244100"},{"key":"e_1_3_5_133_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.01.044"},{"key":"e_1_3_5_134_2","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1002\/hbm.21449","article-title":"Clinical impairment in premanifest and early Huntington's disease is associated with regionally specific atrophy","volume":"34","author":"Scahill RI","year":"2013","unstructured":"Scahill RI et al. 2013 Clinical impairment in premanifest and early Huntington's disease is associated with regionally specific atrophy. Hum. Brain Mapp. 34, 519\u2013529.","journal-title":"Hum. Brain Mapp."},{"key":"e_1_3_5_135_2","doi-asserted-by":"publisher","DOI":"10.4329\/wjr.v6.i6.301"},{"key":"e_1_3_5_136_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2014.00078"},{"key":"e_1_3_5_137_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182648b65"},{"key":"e_1_3_5_138_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.12.042"},{"key":"e_1_3_5_139_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11557"},{"key":"e_1_3_5_140_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2013.01.008"},{"key":"e_1_3_5_141_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5028"},{"key":"e_1_3_5_142_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.10.023"},{"key":"e_1_3_5_143_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2015.02.019"},{"key":"e_1_3_5_144_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1854"},{"key":"e_1_3_5_145_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aam9080"},{"key":"e_1_3_5_146_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.06.019"},{"key":"e_1_3_5_147_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026159"},{"key":"e_1_3_5_148_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.11.009"},{"key":"e_1_3_5_149_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1245296"},{"key":"e_1_3_5_150_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0112413"},{"key":"e_1_3_5_151_2","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.318"},{"key":"e_1_3_5_152_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03241-9"},{"key":"e_1_3_5_153_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1603871113"},{"key":"e_1_3_5_154_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2015.07.013"},{"key":"e_1_3_5_155_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2014.04.005"},{"key":"e_1_3_5_156_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072698"},{"key":"e_1_3_5_157_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3080"},{"key":"e_1_3_5_158_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4699-13.2014"},{"key":"e_1_3_5_159_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912171106"},{"key":"e_1_3_5_160_2","first-page":"15","article-title":"Nigral and extranigral pathology in Parkinson's disease","volume":"46","author":"Braak H","year":"1995","unstructured":"Braak H, Braak E, Yilmazer D, Schultz C, de Vos RA, Jansen EN. 1995 Nigral and extranigral pathology in Parkinson's disease. J. Neural Transm. Suppl. 46, 15\u201331.","journal-title":"J. Neural Transm. Suppl."},{"key":"e_1_3_5_161_2","first-page":"493","article-title":"Changes within the basal nucleus in Parkinson's disease","volume":"317","author":"Ulfig N","year":"1989","unstructured":"Ulfig N, Braak E, Braak H. 1989 Changes within the basal nucleus in Parkinson's disease. Prog. Clin. Biol. Res. 317, 493\u2013500.","journal-title":"Prog. Clin. Biol. Res."},{"key":"e_1_3_5_162_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60492-X"},{"key":"e_1_3_5_163_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2010.52"},{"key":"e_1_3_5_164_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26620"},{"key":"e_1_3_5_165_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26479"},{"key":"e_1_3_5_166_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4564-06.2007"},{"key":"e_1_3_5_167_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2017.12.015"},{"key":"e_1_3_5_168_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.12.023"},{"key":"e_1_3_5_169_2","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.169"},{"key":"e_1_3_5_170_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.12.023"},{"key":"e_1_3_5_171_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25249"},{"key":"e_1_3_5_172_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2015.08.015"},{"key":"e_1_3_5_173_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm4040548"},{"key":"e_1_3_5_174_2","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12526"},{"key":"e_1_3_5_175_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.11.005"},{"key":"e_1_3_5_176_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.03919.x"},{"key":"e_1_3_5_177_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2008.02.015"},{"key":"e_1_3_5_178_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.12.008"},{"key":"e_1_3_5_179_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.08.022"},{"key":"e_1_3_5_180_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3636"},{"key":"e_1_3_5_181_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0040-15.2015"},{"key":"e_1_3_5_182_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2017.75"},{"key":"e_1_3_5_183_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5321.2045"},{"key":"e_1_3_5_184_2","doi-asserted-by":"publisher","DOI":"10.1038\/42166"},{"key":"e_1_3_5_185_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25421"},{"key":"e_1_3_5_186_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1096-7"},{"key":"e_1_3_5_187_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0298-106"},{"key":"e_1_3_5_188_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.03.024"},{"key":"e_1_3_5_189_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31828727ba"},{"key":"e_1_3_5_190_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.10.014"},{"key":"e_1_3_5_191_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000127496.23198.75"},{"key":"e_1_3_5_192_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.67"},{"key":"e_1_3_5_193_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2004.01.007"},{"key":"e_1_3_5_194_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds240"},{"key":"e_1_3_5_195_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.02.013"},{"key":"e_1_3_5_196_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-002-0563-3"},{"key":"e_1_3_5_197_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10648"},{"key":"e_1_3_5_198_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1091-10.2010"},{"key":"e_1_3_5_199_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0075-7"},{"key":"e_1_3_5_200_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2008.07.014"},{"key":"e_1_3_5_201_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.23.13982"},{"key":"e_1_3_5_202_2","doi-asserted-by":"publisher","DOI":"10.1186\/s11689-015-9125-6"},{"key":"e_1_3_5_203_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.31176"},{"key":"e_1_3_5_204_2","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.13418"},{"key":"e_1_3_5_205_2","first-page":"353","article-title":"Alzheimer's disease in Down syndrome","volume":"1","author":"Head E","year":"2012","unstructured":"Head E, Powell D, Gold BT, Schmitt FA. 2012 Alzheimer's disease in Down syndrome. Eur. J. Neurodegener. Dis. 1, 353\u2013364.","journal-title":"Eur. J. Neurodegener. Dis."},{"key":"e_1_3_5_206_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1297"},{"key":"e_1_3_5_207_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1216575110"},{"key":"e_1_3_5_208_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2012.06.020"},{"key":"e_1_3_5_209_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6423"},{"key":"e_1_3_5_210_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.157867"},{"key":"e_1_3_5_211_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2009.09.032"},{"key":"e_1_3_5_212_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2015.11.008"},{"key":"e_1_3_5_213_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-142106"},{"key":"e_1_3_5_214_2","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2011.52"}],"container-title":["Open Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rsob.180138","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/full-xml\/10.1098\/rsob.180138","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rsob.180138","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T23:11:32Z","timestamp":1720566692000},"score":1,"resource":{"primary":{"URL":"https:\/\/royalsocietypublishing.org\/doi\/10.1098\/rsob.180138"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9]]},"references-count":213,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2018,9]]}},"alternative-id":["10.1098\/rsob.180138"],"URL":"https:\/\/doi.org\/10.1098\/rsob.180138","relation":{},"ISSN":["2046-2441"],"issn-type":[{"value":"2046-2441","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9]]},"assertion":[{"value":"2018-03-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"180138"}}