{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T03:39:11Z","timestamp":1791776351984,"version":"4.3.4"},"reference-count":69,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T00:00:00Z","timestamp":1716768000000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["BEAGAL18\/00098"],"award-info":[{"award-number":["BEAGAL18\/00098"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012818","name":"Comunidad de Madrid","doi-asserted-by":"publisher","award":["SI2\/PBG\/2020\u201000014"],"award-info":[{"award-number":["SI2\/PBG\/2020\u201000014"]}],"id":[{"id":"10.13039\/100012818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Comparative Neurology"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In Alzheimer\u00b4s disease (AD), hyperphosphorylated tau spreads along the cerebral cortex in a stereotypical pattern that parallels cognitive deterioration. Tau seems to spread transsynaptically along cortico\u2010cotical pathways that, according to synaptic tract\u2010tracing studies in nonhuman primates, have specific laminar patterns related to the cortical type of the connected areas. This relation is described in the Structural Model. In the present article, we study the laminar distribution of hyperphosphorylated tau, labeled with the antibody AT8, along temporal cortical types in postmortem human brains with different AD stages to test the predictions of the Structural Model. Brains from donors without dementia had scant AT8\u2010immunorreactive (AT8\u2010ir) neurons in allo\u2010, meso\u2010, and isocortical types. In early AD stages, the mesocortical dysgranular type, including part of the transentorhinal cortex, had the highest AT8 immunostaining and AT8\u2010ir neurons density. In advanced AD stages, AT8 immunostaining increased along the isocortical types until reaching the auditory koniocortex. Regarding laminar patterns, in early AD stages there were more AT8\u2010ir neurons in supragranular layers in each de novo involved neocortical type; in advanced AD stages, AT8\u2010ir neurons were equally distributed in supra\u2010 and infragranular layers. These AT8\u2010ir laminar patterns are compatible with the predictions of the Structural Model. In summary, we show that hyperphosphorylated tau initially accumulates in allo\u2010, meso\u2010, and isocortical types, offer a proof of concept for the validity of the Structural Model to predict synaptic pathway organization in the human cerebral cortex, and highlight the relevance of nonhuman primate tract\u2010tracing studies to understand human neuropathology.<\/jats:p>","DOI":"10.1002\/cne.25623","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T01:23:55Z","timestamp":1716859435000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Hyperphosphorylated tau in Alzheimer's disease disseminates along pathways predicted by the Structural Model for Cortico\u2010cortical Connections"],"prefix":"10.1002","volume":"532","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6157-7098","authenticated-orcid":false,"given":"Alicia","family":"Uceda\u2010Heras","sequence":"first","affiliation":[{"name":"Department of Anatomy, Histology and Neuroscience School of Medicine, Aut\u00f3noma University of Madrid  Madrid Spain"},{"name":"PhD Program in Neuroscience UAM\u2010Cajal Aut\u00f3noma University of Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9757-1541","authenticated-orcid":false,"given":"Gonzalo","family":"Aparicio\u2010Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Neuroscience School of Medicine, Aut\u00f3noma University of Madrid  Madrid Spain"},{"name":"Master\u00b4s Program in Neuroscience Aut\u00f3noma University of Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0534-5182","authenticated-orcid":false,"given":"Miguel \u00c1ngel","family":"Garc\u00eda\u2010Cabezas","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Neuroscience School of Medicine, Aut\u00f3noma University of Madrid  Madrid Spain"},{"name":"PhD Program in Neuroscience UAM\u2010Cajal Aut\u00f3noma University of Madrid Madrid Spain"},{"name":"Master\u00b4s Program in Neuroscience Aut\u00f3noma University of Madrid Madrid Spain"},{"name":"Neural Systems Laboratory, Department of Health Sciences Boston University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750\u20103639.2008.00147.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhad104"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14036"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/1.1.103"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902520310"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0149\u20107634(94)00053\u20104"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/7.7.635"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010neuro\u2010071714\u2010033936"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2016.07.003"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2022.08.007"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00936.2017"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.25550"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep43176"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010006\u20100127\u2010z"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0197\u20104580(97)00056\u20100"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010011\u20100825\u2010z"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhy152"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u2010981\u201032\u20109358\u20108_22"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.4436\/jass.91001"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u201012\u2010802395\u20102.00023\u20107"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2015.11.005"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010010\u20100794\u20107"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/1.1.1"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.12585"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429\u2010013\u20100598\u20103"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhw284"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2020.576015"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429\u2010022\u201002548\u20100"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.13706"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2023.1176351"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2006.07.032"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000259"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429\u2010019\u201001841\u20109"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304\u20103940(95)11484\u2010E"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429\u2010023\u201002725\u20109"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2021.118300"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161212799315885"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1162\/netn_a_00100"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2019.0319"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2016.04.017"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1159\/000061462"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21753"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902640306"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u2010642\u201003661\u20103_1"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.901730105"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2363\u201017.2017"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429\u2010020\u201002041\u20106"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22\u201018\u201008117.2002"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460\u20109568.2005.04522.x"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2014.00077"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10980"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2011.12.005"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2015.10.004"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460\u20109568.2005.04299.x"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-34686-9"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2021.790116"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.24650"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/10.9.851"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20108993(79)90485\u20102"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmamm.2023.1241573"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3002365"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2023.1187280"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-86210-6_1"},{"key":"e_1_2_9_66_1","first-page":"137","volume-title":"The primate brain: Advances in primatology","author":"Sanides F.","year":"1970"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00221\u2010005\u20102361\u20103"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14\u201003\u201001856.1994"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2017.04.001"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.04.034"}],"container-title":["Journal of Comparative Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cne.25623","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T14:56:44Z","timestamp":1718117804000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cne.25623"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5]]},"references-count":69,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1002\/cne.25623"],"URL":"https:\/\/doi.org\/10.1002\/cne.25623","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/CNE.25623\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/CNE.25623\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/CNE.25623\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/CNE.25623\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/CNE.25623\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/CNE.25623\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/CNE.25623\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0021-9967","1096-9861"],"issn-type":[{"value":"0021-9967","type":"print"},{"value":"1096-9861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5]]},"assertion":[{"value":"2024-02-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e25623"}}