{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T13:19:19Z","timestamp":1783171159571,"version":"3.54.6"},"reference-count":43,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003792","name":"Brain Foundation","doi-asserted-by":"publisher","award":["FO2022-0083"],"award-info":[{"award-number":["FO2022-0083"]}],"id":[{"id":"10.13039\/501100003792","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009673","name":"Gun and Bertil Stohnes Foundation","doi-asserted-by":"publisher","award":["2023"],"award-info":[{"award-number":["2023"]}],"id":[{"id":"10.13039\/100009673","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008599","name":"Alzheimer Fund","doi-asserted-by":"publisher","award":["AF-980656"],"award-info":[{"award-number":["AF-980656"]}],"id":[{"id":"10.13039\/501100008599","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005701","name":"Maja &amp; JP \u00c5hl\u00e9n Foundation","doi-asserted-by":"publisher","award":["233044"],"award-info":[{"award-number":["233044"]}],"id":[{"id":"10.13039\/501100005701","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004200","name":"Olle Engkvist Foundation","doi-asserted-by":"publisher","award":["215-0399"],"award-info":[{"award-number":["215-0399"]}],"id":[{"id":"10.13039\/501100004200","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021594","name":"The Dementia Foundation","doi-asserted-by":"publisher","award":["2024"],"award-info":[{"award-number":["2024"]}],"id":[{"id":"10.13039\/501100021594","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008444","name":"OE and Edla Johanssons Scientific Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008444","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009487","name":"Swedish Fund for Research Without Animal Experiments","doi-asserted-by":"publisher","award":["F2022-0004"],"award-info":[{"award-number":["F2022-0004"]}],"id":[{"id":"10.13039\/100009487","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006129","name":"King Gustaf V and Queen Victoria&apos;s Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008444","name":"Parkinson&apos;s Foundation","doi-asserted-by":"publisher","award":["1476\/23"],"award-info":[{"award-number":["1476\/23"]}],"id":[{"id":"10.13039\/100008444","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2021-02563"],"award-info":[{"award-number":["2021-02563"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["iScience"],"published-print":{"date-parts":[[2026,5]]},"DOI":"10.1016\/j.isci.2026.115819","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T15:07:36Z","timestamp":1776697656000},"page":"115819","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exposure to fibrillar proteins leads to widespread infiltration but only mild tau pathology in cortical organoids"],"prefix":"10.1016","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3427-8995","authenticated-orcid":false,"given":"Abdulkhalek","family":"Dakhel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Mothes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid","family":"Eltom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech P.","family":"Michno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Erlandsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.isci.2026.115819_bib1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/978-1-0716-2655-9_16","article-title":"A\u03b2 and Tau Prions Causing Alzheimer\u2019s Disease","volume":"2561","author":"Condello","year":"2023","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.isci.2026.115819_bib2","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1097\/WCO.0000000000000349","article-title":"How strong is the evidence that Parkinson\u2019s disease is a prion disorder?","volume":"29","author":"Brundin","year":"2016","journal-title":"Curr. Opin. Neurol."},{"key":"10.1016\/j.isci.2026.115819_bib3","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1007\/s00401-002-0569-x","article-title":"Tau accumulation in astrocytes in progressive supranuclear palsy is a degenerative rather than a reactive process","volume":"104","author":"Togo","year":"2002","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.isci.2026.115819_bib4","first-page":"211","article-title":"Astrocytic Tau Pathologies in Argyrophilic Grain Disease and Related Four-repeat Tauopathies","volume":"72","author":"Ikeda","year":"2018","journal-title":"Acta Med. Okayama"},{"key":"10.1016\/j.isci.2026.115819_bib5","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s40478-023-01589-8","article-title":"Astrocytic uptake of neuronal corpses promotes cell-to-cell spreading of tau pathology","volume":"11","author":"Mothes","year":"2023","journal-title":"Acta Neuropathol. Commun."},{"key":"10.1016\/j.isci.2026.115819_bib6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12974-022-02687-5","article-title":"Intracellular deposits of amyloid-beta influence the ability of human iPSC-derived astrocytes to support neuronal function","volume":"20","author":"Konstantinidis","year":"2023","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.isci.2026.115819_bib7","doi-asserted-by":"crossref","first-page":"11835","DOI":"10.1523\/JNEUROSCI.0983-17.2017","article-title":"Human Astrocytes Transfer Aggregated Alpha-Synuclein via Tunneling Nanotubes","volume":"37","author":"Rostami","year":"2017","journal-title":"J. Neurosci."},{"key":"10.1016\/j.isci.2026.115819_bib8","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1258\/jrsm.2008.08k033","article-title":"Why animal studies are often poor predictors of human reactions to exposure","volume":"102","author":"Bracken","year":"2009","journal-title":"J. R. Soc. Med."},{"key":"10.1016\/j.isci.2026.115819_bib9","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.jacbts.2019.10.008","article-title":"Limitations of Animal Studies for Predicting Toxicity in Clinical Trials: Is it Time to Rethink Our Current Approach?","volume":"4","author":"Van Norman","year":"2019","journal-title":"JACC Basic Transl. Sci."},{"key":"10.1016\/j.isci.2026.115819_bib10","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1038\/nrc1235","article-title":"Comparative biology of mouse versus human cells: modelling human cancer in mice","volume":"3","author":"Rangarajan","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.isci.2026.115819_bib11","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/nature12517","article-title":"Cerebral organoids model human brain development and microcephaly","volume":"501","author":"Lancaster","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.isci.2026.115819_bib12","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.3892\/or.2015.3767","article-title":"Comparison of 2D- and 3D-culture models as drug-testing platforms in breast cancer","volume":"33","author":"Imamura","year":"2015","journal-title":"Oncol. Rep."},{"key":"10.1016\/j.isci.2026.115819_bib13","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3389\/fphar.2018.00006","article-title":"Three-Dimensional in Vitro Cell Culture Models in Drug Discovery and Drug Repositioning","volume":"9","author":"Langhans","year":"2018","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.isci.2026.115819_bib14","doi-asserted-by":"crossref","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":"10.1016\/j.isci.2026.115819_bib15","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1038\/s41593-018-0175-4","article-title":"A 3D human triculture system modeling neurodegeneration and neuroinflammation in Alzheimer\u2019s disease","volume":"21","author":"Park","year":"2018","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.isci.2026.115819_bib16","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1038\/s41380-018-0229-8","article-title":"Modeling amyloid beta and tau pathology in human cerebral organoids","volume":"23","author":"Gonzalez","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"10.1016\/j.isci.2026.115819_bib17","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41531-019-0078-4","article-title":"Modeling Parkinson\u2019s disease in midbrain-like organoids","volume":"5","author":"Smits","year":"2019","journal-title":"npj Parkinson\u2019s Dis."},{"key":"10.1016\/j.isci.2026.115819_bib18","doi-asserted-by":"crossref","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":"10.1016\/j.isci.2026.115819_bib19","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.stemcr.2019.01.020","article-title":"Modeling G2019S-LRRK2 Sporadic Parkinson\u2019s Disease in 3D Midbrain Organoids","volume":"12","author":"Kim","year":"2019","journal-title":"Stem Cell Rep."},{"key":"10.1016\/j.isci.2026.115819_bib20","doi-asserted-by":"crossref","first-page":"5540","DOI":"10.1038\/s41467-020-19264-0","article-title":"APOE4 exacerbates synapse loss and neurodegeneration in Alzheimer\u2019s disease patient iPSC-derived cerebral organoids","volume":"11","author":"Zhao","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.isci.2026.115819_bib21","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.cell.2013.05.057","article-title":"Distinct \u03b1-Synuclein Strains Differentially Promote Tau Inclusions in Neurons","volume":"154","author":"Guo","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.isci.2026.115819_bib22","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s00401-015-1525-x","article-title":"Heterotypic seeding of Tau fibrillization by pre-aggregated Abeta provides potent seeds for prion-like seeding and propagation of Tau-pathology in vivo","volume":"131","author":"Vasconcelos","year":"2016","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.isci.2026.115819_bib23","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1007\/s00401-015-1413-4","article-title":"Templated misfolding of Tau by prion-like seeding along neuronal connections impairs neuronal network function and associated behavioral outcomes in Tau transgenic mice","volume":"129","author":"Stancu","year":"2015","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.isci.2026.115819_bib24","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.60747","article-title":"Application of human liver organoids as a patient-derived primary model for HBV infection and related hepatocellular carcinoma","volume":"10","author":"De Crignis","year":"2021","journal-title":"eLife"},{"key":"10.1016\/j.isci.2026.115819_bib25","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1093\/neuonc\/noaa091","article-title":"Modeling glioblastoma invasion using human brain organoids and single-cell transcriptomics","volume":"22","author":"Krieger","year":"2020","journal-title":"Neuro Oncol."},{"key":"10.1016\/j.isci.2026.115819_bib26","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1038\/s41593-018-0238-6","article-title":"Propagation and spread of pathogenic protein assemblies in neurodegenerative diseases","volume":"21","author":"Jucker","year":"2018","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.isci.2026.115819_bib27","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/j.1750-3639.2012.00627.x","article-title":"Characterization of thorn-shaped astrocytes in white matter of temporal lobe in Alzheimer\u2019s disease brains","volume":"23","author":"L\u00f3pez-Gonz\u00e1lez","year":"2013","journal-title":"Brain Pathol."},{"key":"10.1016\/j.isci.2026.115819_bib28","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.neuron.2011.11.033","article-title":"Propagation of tau pathology in a model of early Alzheimer\u2019s disease","volume":"73","author":"de Calignon","year":"2012","journal-title":"Neuron"},{"key":"10.1016\/j.isci.2026.115819_bib29","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/ncb1901","article-title":"Transmission and spreading of tauopathy in transgenic mouse brain","volume":"11","author":"Clavaguera","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.isci.2026.115819_bib30","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13024-016-0098-z","article-title":"Accumulation of amyloid-\u03b2 by astrocytes result in enlarged endosomes and microvesicle-induced apoptosis of neurons","volume":"11","author":"S\u00f6llvander","year":"2016","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.isci.2026.115819_bib31","doi-asserted-by":"crossref","first-page":"447","DOI":"10.3233\/JAD-180721","article-title":"Tau Biology, Tauopathy, Traumatic Brain Injury, and Diagnostic Challenges","volume":"67","author":"Castellani","year":"2019","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.isci.2026.115819_bib32","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2310057120","article-title":"Shift of the insoluble content of the proteome in the aging mouse brain","volume":"120","author":"Molzahn","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2026.115819_bib33","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s12974-025-03433-3","article-title":"A 3D human iPSC-derived multi-cell type neurosphere system to model cellular responses to chronic amyloidosis","volume":"22","author":"Wendt","year":"2025","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.isci.2026.115819_bib34","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1096\/fj.11-199851","article-title":"Identification of oligomers at early stages of tau aggregation in Alzheimer\u2019s disease","volume":"26","author":"Lasagna-Reeves","year":"2012","journal-title":"FASEB J."},{"key":"10.1016\/j.isci.2026.115819_bib35","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s00401-024-02729-7","article-title":"Identification of high-performing antibodies for the reliable detection of Tau proteoforms by Western blotting and immunohistochemistry","volume":"147","author":"Ellis","year":"2024","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.isci.2026.115819_bib36","doi-asserted-by":"crossref","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":"10.1016\/j.isci.2026.115819_bib37","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1111\/brv.12626","article-title":"Modelling neurodegenerative diseases with 3D brain organoids","volume":"95","author":"Chang","year":"2020","journal-title":"Biol. Rev."},{"key":"10.1016\/j.isci.2026.115819_bib38","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2021.109042","article-title":"5-hydroxymethylcytosine is dynamically regulated during forebrain organoid development and aberrantly altered in Alzheimer\u2019s disease","volume":"35","author":"Kuehner","year":"2021","journal-title":"Cell Rep."},{"key":"10.1016\/j.isci.2026.115819_bib39","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1212\/01.wnl.0000219668.47116.e6","article-title":"Neuropathology of older persons without cognitive impairment from two community-based studies","volume":"66","author":"Bennett","year":"2006","journal-title":"Neurology"},{"key":"10.1016\/j.isci.2026.115819_bib40","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s00401-013-1157-y","article-title":"Non-Alzheimer neurodegenerative pathologies and their combinations are more frequent than commonly believed in the elderly brain: a community-based autopsy series","volume":"126","author":"Kovacs","year":"2013","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.isci.2026.115819_bib41","doi-asserted-by":"crossref","first-page":"5155","DOI":"10.1007\/s12035-023-03387-8","article-title":"The Role of Tau Proteoforms in Health and Disease","volume":"60","author":"Waheed","year":"2023","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.isci.2026.115819_bib42","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.scr.2016.12.006","article-title":"Derivation of human iPS cell lines from monozygotic twins in defined and xeno free conditions","volume":"18","author":"Uhlin","year":"2017","journal-title":"Stem Cell Res."},{"key":"10.1016\/j.isci.2026.115819_bib43","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0029597","article-title":"Capture of neuroepithelial-like stem cells from pluripotent stem cells provides a versatile system for in vitro production of human neurons","volume":"7","author":"Falk","year":"2012","journal-title":"PLoS One"}],"container-title":["iScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004226011946?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004226011946?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T12:44:16Z","timestamp":1783169056000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589004226011946"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":43,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["S2589004226011946"],"URL":"https:\/\/doi.org\/10.1016\/j.isci.2026.115819","relation":{},"ISSN":["2589-0042"],"issn-type":[{"value":"2589-0042","type":"print"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Exposure to fibrillar proteins leads to widespread infiltration but only mild tau pathology in cortical organoids","name":"articletitle","label":"Article Title"},{"value":"iScience","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.isci.2026.115819","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"115819"}}