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Involvement of the ...
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Delvenne, AuroreDepartment of Psychiatry and Neuropsychology, Alzheimer Centrum Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
(författare)
Involvement of the choroid plexus in Alzheimer's disease pathophysiology : findings from mouse and human proteomic studies
- Artikel/kapitelEngelska2024
Förlag, utgivningsår, omfång ...
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BioMed Central (BMC),2024
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:oru-115207
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https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-115207URI
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https://doi.org/10.1186/s12987-024-00555-3DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
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The present study was supported by Alzheimer Nederland grant number WE.15‑2022‑01, the Research Foundation Flanders (FWO Vlaanderen; 1295223N, 1157621N and 1195019N), and partly supported by ZonMw (the Netherlands Organization for Health Research and Development) grant numbers 733050502 and 7330505021, an anonymous foundation and EMIF‑AD. The EMIF‑AD project has received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement n° 115372, resources of which are composed of financial contribution from the European Union’s Seventh Framework Program (FP7/2007‑2013) and EFPIA companies’ in kind contribution.
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Background: Structural and functional changes of the choroid plexus (ChP) have been reported in Alzheimer's disease (AD). 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.Methods: We used an APP knock-in mouse model, APPNL-G-F, 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 weeks (n = 5) and 40 weeks (n = 5). Results were compared with previously published human AD CSF proteomic data (n = 496) to identify key proteins and pathways associated with ChP changes in AD.Results: ChP tissue proteome was dysregulated in APPNL-G-F mice relative to wild-type mice at both 7 and 40 weeks. 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 weeks, while pathways associated with nervous system, immune system, protein degradation and vascular system were uniquely dysregulated at 40 weeks. CSF proteomics in both mice and humans showed similar ChP-related dysregulated pathways.Conclusions: 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.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Vandendriessche, CharysseVIB Center for Inflammation Research, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
(författare)
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Gobom, JohanClinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
(författare)
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Burgelman, MarliesVIB Center for Inflammation Research, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
(författare)
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Dujardin, PieterVIB Center for Inflammation Research, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
(författare)
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De Nolf, ClintDepartment of Biomedical Molecular Biology, Ghent University, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
(författare)
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Tijms, Betty M.Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands
(författare)
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Teunissen, Charlotte E.Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam University Medical Centers (AUMC), Amsterdam Neuroscience, Amsterdam, Netherlands
(författare)
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Schindler, Suzanne E.Department of Neurology, Washington University School of Medicine, St. Louis, USA; Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St. Louis, USA
(författare)
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Verhey, FransDepartment of Psychiatry and Neuropsychology, Alzheimer Centrum Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
(författare)
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Ramakers, InezDepartment of Psychiatry and Neuropsychology, Alzheimer Centrum Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
(författare)
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Martinez-Lage, PabloFundación CITA-Alzhéimer Fundazioa, San Sebastian, Spain
(författare)
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Tainta, MikelFundación CITA-Alzhéimer Fundazioa, San Sebastian, Spain
(författare)
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Vandenberghe, RikNeurology Service, University Hospitals Leuven, Louvain, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Louvain, Belgium
(författare)
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Schaeverbeke, JolienNeurology Service, University Hospitals Leuven, Louvain, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Louvain, Belgium
(författare)
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Engelborghs, SebastiaanReference Center for Biological Markers of Dementia (BIODEM), Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Department of Neurology and Bru-BRAIN, Universitair Ziekenhuis Brussel, Brussels, Belgium; NEUR Research Group, Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium
(författare)
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De Roeck, EllenReference Center for Biological Markers of Dementia (BIODEM), Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium
(författare)
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Popp, JuliusOld Age Psychiatry, University Hospital Lausanne, Lausanne, Switzerland; Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatry University Hospital Zürich, Zurich, Switzerland
(författare)
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Peyratout, GwendolineOld Age Psychiatry, University Hospital Lausanne, Lausanne, Switzerland
(författare)
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Tsolaki, Magda1st Department of Neurology, AHEPA University Hospital, Medical School, Faculty of Health Sciences, Aristotle University of Thessaloniki, Makedonia, Thessaloniki, Greece
(författare)
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Freund-Levi, Yvonne,1956-Örebro universitet,Institutionen för medicinska vetenskaper,Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden; Department of Psychiatry in Region Örebro County and School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Old Age Psychiatry, Psychology & Neuroscience, King’s College, London, UK(Swepub:oru)yfi
(författare)
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Lovestone, SimonJohnson and Johnson Medical Ltd., Wokingham, UK; University of Oxford, Oxford, UK
(författare)
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Streffer, JohannesReference Center for Biological Markers of Dementia (BIODEM), Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; H. Lundbeck A/S, Valby, Denmark
(författare)
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Bertram, LarsLübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany
(författare)
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Blennow, KajClinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France; Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, and Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, People’s Republic of China
(författare)
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Zetterberg, HenrikClinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK; UK Dementia Research Institute at UCL, London, UK; Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China; Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison WI, USA
(författare)
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Visser, Pieter JelleDepartment of Psychiatry and Neuropsychology, Alzheimer Centrum Limburg, School for Mental Health and Neuroscience, Maastricht University, P.O. Box 616, Maastricht, 6200 MD, The Netherlands; Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands; Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden
(författare)
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Vandenbroucke, Roosmarijn E.VIB Center for Inflammation Research, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
(författare)
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Vos, Stephanie J. B.Department of Psychiatry and Neuropsychology, Alzheimer Centrum Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
(författare)
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Department of Psychiatry and Neuropsychology, Alzheimer Centrum Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The NetherlandsVIB Center for Inflammation Research, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Fluids and Barriers of the CNS: BioMed Central (BMC)21:12045-8118
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Delvenne, Aurore
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Vandendriessche, ...
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Gobom, Johan
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Burgelman, Marli ...
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Dujardin, Pieter
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De Nolf, Clint
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Tijms, Betty M.
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Teunissen, Charl ...
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Schindler, Suzan ...
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Verhey, Frans
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Ramakers, Inez
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Martinez-Lage, P ...
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Tainta, Mikel
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Vandenberghe, Ri ...
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Schaeverbeke, Jo ...
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Engelborghs, Seb ...
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De Roeck, Ellen
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Popp, Julius
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Peyratout, Gwend ...
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Tsolaki, Magda
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Freund-Levi, Yvo ...
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Lovestone, Simon
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Streffer, Johann ...
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Bertram, Lars
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Blennow, Kaj
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Zetterberg, Henr ...
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Visser, Pieter J ...
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