{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:11:46Z","timestamp":1790665906733,"version":"4.1.0"},"reference-count":66,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,12,26]],"date-time":"2023-12-26T00:00:00Z","timestamp":1703548800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81941012"],"award-info":[{"award-number":["81941012"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31970510"],"award-info":[{"award-number":["31970510"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017510","name":"UK Dementia Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>The \u201cprion\u2010like\u201d features of Alzheimer's disease (AD) tauopathy and its relationship with amyloid\u2010\u03b2 (A\u03b2) have never been experimentally studied in primates phylogenetically close to humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We injected 17 macaques in the entorhinal cortex with nanograms of seeding\u2010competent tau aggregates purified from AD brains or control extracts from aged\u2010matched healthy brains, with or without intracerebroventricular co\u2010injections of oligomeric\u2010A\u03b2.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Pathological tau injection increased cerebrospinal fluid (CSF) p\u2010tau181 concentration after 18 months. Tau pathology spreads from the entorhinal cortex to the hippocampal trisynaptic loop and the cingulate cortex, resuming the experimental progression of Braak stage I to IV. Many AD\u2010related molecular networks were impacted by tau seeds injections regardless of A\u03b2 injections in proteomic analyses. However, we found mature neurofibrillary tangles, increased CSF total\u2010tau concentration, and pre\u2010 and postsynaptic degeneration only in A\u03b2 co\u2010injected macaques.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Oligomeric\u2010A\u03b2 mediates the maturation of tau pathology and its neuronal toxicity in macaques but not its initial spreading.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>This study supports the \u201cprion\u2010like\u201d properties of misfolded tau extracted from AD brains.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This study empirically validates the Braak staging in an anthropomorphic brain.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This study highlights the role of oligomeric A\u03b2 in driving the maturation and toxicity of tau pathology.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This work establishes a novel animal model of early sporadic AD that is closer to the human pathology.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.13604","type":"journal-article","created":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T02:49:25Z","timestamp":1703645365000},"page":"1894-1912","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Tau seeds from Alzheimer's disease brains trigger tau spread in macaques while oligomeric\u2010A\u03b2 mediates pathology maturation"],"prefix":"10.1002","volume":"20","author":[{"given":"Morgane","family":"Darricau","sequence":"first","affiliation":[{"name":"Univ. Bordeaux, CNRS Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changsong","family":"Dou","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Human Disease Comparative Medicine Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases National Center for Technology and Innovation of Animal Model Institute of Laboratory Animal Sciences Chinese Academy of Medical Sciences (CAMS)  Beijing P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remi","family":"Kinet","sequence":"additional","affiliation":[{"name":"Univ. Bordeaux, CNRS Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhu","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Human Disease Comparative Medicine Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases National Center for Technology and Innovation of Animal Model Institute of Laboratory Animal Sciences Chinese Academy of Medical Sciences (CAMS)  Beijing P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhou","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Human Disease Comparative Medicine Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases National Center for Technology and Innovation of Animal Model Institute of Laboratory Animal Sciences Chinese Academy of Medical Sciences (CAMS)  Beijing P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianglei","family":"Li","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Human Disease Comparative Medicine Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases National Center for Technology and Innovation of Animal Model Institute of Laboratory Animal Sciences Chinese Academy of Medical Sciences (CAMS)  Beijing P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Bedel","sequence":"additional","affiliation":[{"name":"CHU de Bordeaux Service de biochimie, Bordeaux Univ. Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Claverol","sequence":"additional","affiliation":[{"name":"Univ. Bordeaux, Bordeaux Proteome  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Tokarski","sequence":"additional","affiliation":[{"name":"Univ. Bordeaux, Bordeaux Proteome  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taxiarchis","family":"Katsinelos","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute Department of Clinical Neurosciences University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"McEwan","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute Department of Clinical Neurosciences University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Human Disease Comparative Medicine Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases National Center for Technology and Innovation of Animal Model Institute of Laboratory Animal Sciences Chinese Academy of Medical Sciences (CAMS)  Beijing P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Gao","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Human Disease Comparative Medicine Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases National Center for Technology and Innovation of Animal Model Institute of Laboratory Animal Sciences Chinese Academy of Medical Sciences (CAMS)  Beijing P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Bourdenx","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Dehay","sequence":"additional","affiliation":[{"name":"Univ. Bordeaux, CNRS Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Qin","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Human Disease Comparative Medicine Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases National Center for Technology and Innovation of Animal Model Institute of Laboratory Animal Sciences Chinese Academy of Medical Sciences (CAMS)  Beijing P.R. China"},{"name":"Changping National laboratory (CPNL)  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwan","family":"Bezard","sequence":"additional","affiliation":[{"name":"Univ. Bordeaux, CNRS Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives  Bordeaux France"},{"name":"Motac Neuroscience  Floirac France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Planche","sequence":"additional","affiliation":[{"name":"Univ. Bordeaux, CNRS Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives  Bordeaux France"},{"name":"CHU de Bordeaux, P\u00f4le de Neurosciences Cliniques Centre M\u00e9moire de Ressources et de Recherche  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12638"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.10.007"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1566067"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583\u2010021\u201000533\u2010w"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010015\u20101390\u20107"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.209296"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1901"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1301175110"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160833"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1230\u201017.2017"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aau5732"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1255555"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.11.033"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010018\u20100235\u20109"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010021\u201001309\u20106"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abh1448"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201034129\u20104"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e318232a379"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4443"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478\u2010022\u201001410\u2010y"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2015.09.018"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010020\u20100687\u20106"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212948"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.13239"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010016\u20101662\u2010x"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478\u2010019\u20100682\u2010x"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajp.23254"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/bf00308809"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.15.5827"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403015101"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.04.056"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1607215114"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep22728"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2021.07.009"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx120"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478\u2010019\u20100771\u2010x"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp101"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt019"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592\u2010019\u20100470\u20103"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac428"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210207200"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911829107"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1353\u201014.2014"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1902301116"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000201479"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161212799315885"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10051138"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bj.2018.01.003"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2020.01.011"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469\u20107580.2007.00764.x"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478\u2010015\u20100199\u2010x"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606210"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12192"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(18)30490\u20103"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.04.020"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.3530"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010021\u201000474\u2010z"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.04.031"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010021\u201000999\u2010y"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12318"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2017.11.005"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12321"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhy152"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.13604","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T11:53:24Z","timestamp":1759924404000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.13604"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,26]]},"references-count":66,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/alz.13604"],"URL":"https:\/\/doi.org\/10.1002\/alz.13604","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,26]]},"assertion":[{"value":"2023-07-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}