{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T20:23:11Z","timestamp":1782591791411,"version":"3.54.5"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>The choroid plexus (ChP) is a specialised tissue of the central nervous system that produces cerebrospinal fluid (CSF), maintains cerebral homeostasis and forms the blood-CSF barrier (B-CSF-B), a key interface that regulates the exchange of substances between the blood and the brain. Despite its physiological importance, the involvement of the ChP in neurodegenerative diseases such as Alzheimer\u2019s disease (AD), remains poorly understood. This is largely due to the reliance on murine models and the limited availability of human brain tissue. Recent advances in human stem-cell derived ChP organoids now offer a more physiologically relevant model to interrogate ChP role in human health and disease. Given that in AD pathology beta-amyloid (A\u03b2) accumulation has been linked to early disruption of brain barriers, studying the B-CSF-B is particularly relevant. Transthyretin (TTR), the predominant protein secreted by the ChP, is thought to play a role in the transport and clearance of A\u03b2, although its exact mechanisms are not yet fully elucidated. Here, we propose the use of ChP organoids to investigate the role of the B-CSF-B in amyloid uptake which may contribute to barrier dysfunction and disease progression in AD.<\/jats:p>","DOI":"10.3389\/fncel.2026.1769911","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T05:34:03Z","timestamp":1771392843000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Choroid plexus organoids mimic amyloid uptake at the blood-cerebrospinal fluid-barrier"],"prefix":"10.3389","volume":"20","author":[{"given":"C.","family":"Municio","sequence":"first","affiliation":[{"name":"Neurobiology of Alzheimer\u2019s Disease Unit, Functional Unit for Research into Chronic Diseases, Network Centre for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Sapidou","sequence":"additional","affiliation":[{"name":"Centre for Developmental Neurobiology, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. J.","family":"Apsley","sequence":"additional","affiliation":[{"name":"Centre for Developmental Neurobiology, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Fernandez-Otero","sequence":"additional","affiliation":[{"name":"Centre for Developmental Neurobiology, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. E.","family":"Arber","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Wray","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Carro","sequence":"additional","affiliation":[{"name":"Neurobiology of Alzheimer\u2019s Disease Unit, Functional Unit for Research into Chronic Diseases, Network Centre for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Pellegrini","sequence":"additional","affiliation":[{"name":"Centre for Developmental Neurobiology, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"219","DOI":"10.2174\/1874609811003030219","article-title":"Clearance of amyloid-\u03b2 peptide across the choroid plexus in Alzheimer\u2019s disease","volume":"3","author":"Alvira-Botero","year":"2010","journal-title":"Curr. Aging Sci."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"87","DOI":"10.3389\/fnagi.2019.00087","article-title":"Decreased cerebrospinal fluid flow is associated with cognitive deficit in elderly patients","volume":"11","author":"Attier-Zmudka","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1038\/s41380-022-01623-6","article-title":"Deconstructing the functional neuroanatomy of the choroid plexus: an ontogenetic perspective for studying neurodevelopmental and neuropsychiatric disorders","volume":"27","author":"Bitanihirwe","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1390","DOI":"10.1038\/nm1202-793","article-title":"Serum insulin-like growth factor I regulates brain amyloid-beta levels","volume":"8","author":"Carro","year":"2002","journal-title":"Nat. Med."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1179\/016164106X98035","article-title":"Comparative proteomics of cerebrospinal fluid in neuropathologically-confirmed Alzheimer\u2019s disease and non-demented elderly subjects","volume":"28","author":"Casta\u00f1o","year":"2006","journal-title":"Neurol. Res."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1177\/153537020523001011","article-title":"The choroid plexus removes beta-amyloid from brain cerebrospinal fluid","volume":"230","author":"Crossgrove","year":"2005","journal-title":"Exp. Biol. Med. (Maywood)"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"3056.e21","DOI":"10.1016\/j.cell.2021.04.003","article-title":"A cellular and spatial map of the choroid plexus across brain ventricles and ages","volume":"184","author":"Dani","year":"2021","journal-title":"Cell"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.2967\/jnumed.116.187211","article-title":"Cerebrospinal fluid clearance in Alzheimer disease measured with dynamic PET","volume":"58","author":"de Leon","year":"2017","journal-title":"J. Nucl. Med."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.neuron.2004.07.017","article-title":"LRP\/amyloid beta-peptide interaction mediates differential brain efflux of Abeta isoforms","volume":"43","author":"Deane","year":"2004","journal-title":"Neuron"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s12987-024-00555-3","article-title":"Involvement of the choroid plexus in Alzheimer's disease pathophysiology: findings from mouse and human proteomic studies","volume":"21","author":"Delvenne","year":"2024","journal-title":"Fluids Barriers CNS"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1007\/s00401-006-0115-3","article-title":"RAGE, LRP-1, and amyloid-beta protein in Alzheimer\u2019s disease","volume":"112","author":"Donahue","year":"2006","journal-title":"Acta Neuropathol."},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1111\/jne.12432","article-title":"Sex hormone decline and amyloid \u03b2 synthesis, transport and clearance in the brain","volume":"28","author":"Duarte","year":"2016","journal-title":"J. Neuroendocrinol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"146561","DOI":"10.1016\/j.brainres.2019.146561","article-title":"Back to the origins: human brain organoids to investigate neurodegeneration","volume":"1727","author":"Faravelli","year":"2020","journal-title":"Brain Res."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"2578","DOI":"10.1038\/s41591-025-03831-3","article-title":"Disruption of the cerebrospinal fluid-plasma protein balance in cognitive impairment and aging","volume":"31","author":"Farinas","year":"2025","journal-title":"Nat. Med."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1007\/s00401-018-1807-1","article-title":"Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease","volume":"135","author":"Ghersi-Egea","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10020224","article-title":"Choroid plexus in Alzheimer\u2019s disease-the current state of knowledge","volume":"10","author":"Gi\u00e3o","year":"2022","journal-title":"Biomedicine"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3233\/jad-2008-14102","article-title":"Quantitative analysis of transthyretin, tau and amyloid-beta in patients with dementia","volume":"14","author":"Gloeckner","year":"2008","journal-title":"J Alzheimer\u2019s Dis"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3389\/fncel.2015.00017","article-title":"Choroid plexus dysfunction impairs beta-amyloid clearance in a triple transgenic mouse model of Alzheimer\u2019s disease","volume":"9","author":"Gonz\u00e1lez-Marrero","year":"2015","journal-title":"Front. Cell. Neurosci."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s12031-002-0008-4","article-title":"The role of the low-density lipoprotein receptor-related protein (LRP1) in Alzheimer\u2019s a beta generation: development of a cell-based model system","volume":"19","author":"Goto","year":"2002","journal-title":"J. Mol. Neurosci."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s13024-020-00391-7","article-title":"Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer\u2019s disease","volume":"15","author":"Guo","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"469","DOI":"10.2174\/156800705774322102","article-title":"Low density lipoprotein receptor-related proteins (LRPs), Alzheimer\u2019s and cognition","volume":"4","author":"Harris-White","year":"2005","journal-title":"Curr. Drug Targets CNS Neurol. Disord."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"15","DOI":"10.2174\/156720508783884675","article-title":"Functional role of lipoprotein receptors in Alzheimer\u2019s disease","volume":"5","author":"Jaeger","year":"2008","journal-title":"Curr. Alzheimer Res."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s12987-018-0120-7","article-title":"Choroid plexus genes for CSF production and brain homeostasis are altered in Alzheimer\u2019s disease","volume":"15","author":"Kant","year":"2018","journal-title":"Fluids Barriers CNS"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"eadv8269","DOI":"10.1126\/science.adv8269","article-title":"Glymphatic dysfunction in Alzheimer\u2019s disease: a critical appraisal","volume":"389","author":"Keil","year":"2025","journal-title":"Science"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"2329","DOI":"10.1038\/nprot.2014.158","article-title":"Generation of cerebral organoids from human pluripotent stem cells","volume":"9","author":"Lancaster","year":"2014","journal-title":"Nat. Protoc."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"813","DOI":"10.3233\/JAD-160722","article-title":"Cerebrospinal fluid A\u03b242\/40 corresponds better than A\u03b242 to amyloid PET in Alzheimer\u2019s disease","volume":"55","author":"Lewczuk","year":"2017","journal-title":"J Alzheimer\u2019s Dis"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"949231","DOI":"10.3389\/fnmol.2022.949231","article-title":"Choroid plexus epithelium and its role in neurological diseases","volume":"15","author":"Liu","year":"2022","journal-title":"Front. Mol. Neurosci."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/1750-1326-4-17","article-title":"LRP1 shedding in human brain: roles of ADAM10 and ADAM17","volume":"4","author":"Liu","year":"2009","journal-title":"Mol. Neurodegener."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/nrn3921","article-title":"Development and functions of the choroid plexus-cerebrospinal fluid system","volume":"16","author":"Lun","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"5149","DOI":"10.1038\/s41467-025-60361-9","article-title":"Sequential emergence and contraction of epithelial subtypes in the prenatal human choroid plexus revealed by a stem cell model","volume":"16","author":"Masters","year":"2025","journal-title":"Nat. Commun."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3389\/fncel.2012.00025","article-title":"Modulation of iron metabolism in aging and in Alzheimer\u2019s disease: relevance of the choroid plexus","volume":"6","author":"Mesquita","year":"2012","journal-title":"Front. Cell. Neurosci."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"269","DOI":"10.2174\/1567205053585918","article-title":"LRP-mediated clearance of A\u03b2 is inhibited by KPI-containing isoforms of APP","volume":"2","author":"Moir","year":"2005","journal-title":"Curr. Alzheimer Res."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"878","DOI":"10.3390\/ijms24010878","article-title":"Choroid plexus Aquaporin\u2019s in CSF homeostasis and the Glymphatic system: their relevance for Alzheimer\u2019s disease","volume":"24","author":"Municio","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/2045-8118-8-21","article-title":"Amyloid-beta transporter expression at the blood-CSF barrier is age-dependent","volume":"8","author":"Pascale","year":"2011","journal-title":"Fluids Barriers CNS"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"eaaz5626","DOI":"10.1126\/science.aaz5626","article-title":"Human CNS barrier-forming organoids with cerebrospinal fluid production","volume":"369","author":"Pellegrini","year":"2020","journal-title":"Science"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.ceb.2021.05.005","article-title":"Breaking the barrier: in vitro models to study choroid plexus development","volume":"73","author":"Pellegrini","year":"2021","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"3483","DOI":"10.14336\/AD.2024.1409","article-title":"Pros and cons of human brain organoids to study Alzheimer\u2019s disease","volume":"16","author":"Sainz","year":"2024","journal-title":"Aging Dis."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.yfrne.2016.12.002","article-title":"The choroid plexus as a sex hormone target: functional implications","volume":"44","author":"Santos","year":"2017","journal-title":"Front. Neuroendocrinol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1152\/physrev.00060.2021","article-title":"The choroid plexus: a missing link in our understanding of brain development and function","volume":"103","author":"Saunders","year":"2023","journal-title":"Physiol. Rev."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/s40364-025-00829-4","article-title":"Bridging the barrier: insights into blood biomarkers and therapeutic strategies targeting choroid plexus and BBB dysfunction in Alzheimer\u2019s disease","volume":"13","author":"Sharma","year":"2025","journal-title":"Biomark. Res."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1016\/s1474-4422(03)00487-3","article-title":"Alzheimer's disease, normal-pressure hydrocephalus, and senescent changes in CSF circulatory physiology: a hypothesis","volume":"2","author":"Silverberg","year":"2003","journal-title":"Lancet Neurol."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1097\/NEN.0b013e3181c8ad2f","article-title":"Amyloid deposition and influx transporter expression at the blood-brain barrier increase in normal aging","volume":"69","author":"Silverberg","year":"2010","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"4578","DOI":"10.1093\/bioinformatics\/btab503","article-title":"UCSC cell browser: visualize your single-cell data","volume":"37","author":"Speir","year":"2021","journal-title":"Bioinformatics"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/7651_2024_601","article-title":"Functional imaging methods for investigating 3D choroid plexus organoids","author":"Tang","year":"2025","journal-title":"Methods Mol. Biol."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1016\/j.neurobiolaging.2008.08.017","article-title":"Abeta accumulation in choroid plexus is associated with mitochondrial-induced apoptosis","volume":"31","author":"Vargas","year":"2010","journal-title":"Neurobiol. Aging"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"e70239","DOI":"10.1002\/alz.70239","article-title":"Choroid plexus free-water correlates with glymphatic function in Alzheimer\u2019s disease","volume":"21","author":"Xu","year":"2025","journal-title":"Alzheimers Dement."},{"key":"ref47","doi-asserted-by":"publisher","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."}],"container-title":["Frontiers in Cellular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2026.1769911\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T05:34:04Z","timestamp":1771392844000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2026.1769911\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,18]]},"references-count":47,"alternative-id":["10.3389\/fncel.2026.1769911"],"URL":"https:\/\/doi.org\/10.3389\/fncel.2026.1769911","relation":{},"ISSN":["1662-5102"],"issn-type":[{"value":"1662-5102","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,18]]},"article-number":"1769911"}}