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Nonetheless, the role of the ChP in the pathogenesis of AD remains largely unknown. We aim to unravel the relation between ChP functioning and core AD pathogenesis using a unique proteomic approach in mice and humans.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used an APP knock-in mouse model, APP\n                      <jats:sup>NL-G-F<\/jats:sup>\n                      , exhibiting amyloid pathology, to study the association between AD brain pathology and protein changes in mouse ChP tissue and CSF using liquid chromatography mass spectrometry. Mouse proteomes were investigated at the age of 7\u00a0weeks (n\u2009=\u20095) and 40\u00a0weeks (n\u2009=\u20095). Results were compared with previously published human AD CSF proteomic data (n\u2009=\u2009496) to identify key proteins and pathways associated with ChP changes in AD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ChP tissue proteome was dysregulated in APP\n                      <jats:sup>NL-G-F<\/jats:sup>\n                      mice relative to wild-type mice at both 7 and 40\u00a0weeks. At both ages, ChP tissue proteomic changes were associated with epithelial cells, mitochondria, protein modification, extracellular matrix and lipids. Nonetheless, some ChP tissue proteomic changes were different across the disease trajectory; pathways related to lysosomal function, endocytosis, protein formation, actin and complement were uniquely dysregulated at 7\u00a0weeks, while pathways associated with nervous system, immune system, protein degradation and vascular system were uniquely dysregulated at 40\u00a0weeks. CSF proteomics in both mice and humans showed similar ChP-related dysregulated pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Together, our findings support the hypothesis of ChP dysfunction in AD. These ChP changes were related to amyloid pathology. Therefore, the ChP could become a novel promising therapeutic target for AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12987-024-00555-3","type":"journal-article","created":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T19:02:05Z","timestamp":1721242925000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Involvement of the choroid plexus in Alzheimer\u2019s disease pathophysiology: findings from mouse and human proteomic studies"],"prefix":"10.1186","volume":"21","author":[{"given":"Aurore","family":"Delvenne","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charysse","family":"Vandendriessche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Gobom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlies","family":"Burgelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Dujardin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clint","family":"De Nolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty M.","family":"Tijms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte E.","family":"Teunissen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne E.","family":"Schindler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans","family":"Verhey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inez","family":"Ramakers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Martinez-Lage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikel","family":"Tainta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rik","family":"Vandenberghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolien","family":"Schaeverbeke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiaan","family":"Engelborghs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"De Roeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius","family":"Popp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwendoline","family":"Peyratout","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magda","family":"Tsolaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Freund-Levi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Lovestone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Streffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Bertram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter Jelle","family":"Visser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roosmarijn E.","family":"Vandenbroucke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie J. 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All centers approved participation in this study after local medical ethics committee approval.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Ms. Delvenne received funding from Alzheimer Nederland (grant number WE.15-2022-01). Dr. Schindler has served on advisory boards for Eisai. The institution of Dr. Vandenberghe has clinical trial agreements (RV as PI) with Alector, Biogen, Denali, EliLilly, J&J, UCB. The institution of Dr. Vandenberghe has consultancy agreements (RV as DSMB member) with AC Immune. Dr. Schaeverbeke is a senior postdoctoral fellow [12Y1623N] of FWO. Dr. Schaeverbeke receives funding from Stichting Alzheimer Onderzoek [SAO-FRA 2021\/0022]. Dr. Popp served as a consultant and at advisory boards for the Nestl\u00e9 Institute of Health Sciences, Ono Pharma, OM Pharma, Schwabe Pharma, Lilly, Roche, and Fujirebio Europe. All his disclosures are unrelated to the present work. The VD cohort was supported by grants from the Swiss National Research Foundation (SNF 320030_204886), Synapsis Foundation\u2014Dementia Research Switzerland (Grant number 2017-PI01). Dr. Blennow has served as a consultant and at advisory boards for AC Immune, Acumen, ALZPath, AriBio, BioArctic, Biogen, Eisai, Lilly, Moleac Pte. Ltd, Novartis, Ono Pharma, Prothena, Roche Diagnostics, and Siemens Healthineers; has served at data monitoring committees for Julius Clinical and Novartis; has given lectures, produced educational materials and participated in educational programs for AC Immune, Biogen, Celdara Medical, Eisai and Roche Diagnostics; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. Dr. Zetterberg has served at scientific advisory boards and\/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). Dr. Visser received funding from the European Commission, IMI 2 Joint Undertaking (JU), AMYPAD, grant n\u00b0 115952; European Commission, IMI 2 JU, RADAR-AD, grant n\u00b0806999; European Commission, IMI 2 JU, EPND, grant n\u00b0101034344. The IMI JU receives support from the European Union\u2019s Horizon 2020 research and innovation programme and EFPIA. Dr. Visser received also funding from Zon-MW, Redefining Alzheimer's disease, grant n\u00b0733050824736; and Biogen (Amyloid biomarker study group). Grants were paid to the university. Dr. Vos received funding from ZonMW (SNAP VIMP grant n\u00b07330505021), Stichting Adriana van Rinsum-Ponssen, and the EPND project, which received funding from the European Commision, IMI 2 Joint Undertaking (JU) under grant agreement n\u00b0101034344. The IMI JU receives support from the European Union\u2019s Horizon 2020 research and innovation programme and EFPIA. All others authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"58"}}