Titre
Involvement of the choroid plexus in Alzheimer's disease pathophysiology: findings from mouse and human proteomic studies.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Delvenne, A.
Auteure/Auteur
Vandendriessche, C.
Auteure/Auteur
Gobom, J.
Auteure/Auteur
Burgelman, M.
Auteure/Auteur
Dujardin, P.
Auteure/Auteur
De Nolf, C.
Auteure/Auteur
Tijms, B.M.
Auteure/Auteur
Teunissen, C.E.
Auteure/Auteur
Schindler, S.E.
Auteure/Auteur
Verhey, F.
Auteure/Auteur
Ramakers, I.
Auteure/Auteur
Martinez-Lage, P.
Auteure/Auteur
Tainta, M.
Auteure/Auteur
Vandenberghe, R.
Auteure/Auteur
Schaeverbeke, J.
Auteure/Auteur
Engelborghs, S.
Auteure/Auteur
De Roeck, E.
Auteure/Auteur
Popp, J.
Auteure/Auteur
Peyratout, G.
Auteure/Auteur
Tsolaki, M.
Auteure/Auteur
Freund-Levi, Y.
Auteure/Auteur
Lovestone, S.
Auteure/Auteur
Streffer, J.
Auteure/Auteur
Bertram, L.
Auteure/Auteur
Blennow, K.
Auteure/Auteur
Zetterberg, H.
Auteure/Auteur
Visser, P.J.
Auteure/Auteur
Vandenbroucke, R.E.
Auteure/Auteur
Vos, SJB
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
2045-8118
Statut éditorial
Publié
Date de publication
2024-07-18
Volume
21
Numéro
1
Première page
58
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
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.
We used an APP knock-in mouse model, APP <sup>NL-G-F</sup> , 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.
ChP tissue proteome was dysregulated in APP <sup>NL-G-F</sup> 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.
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.
We used an APP knock-in mouse model, APP <sup>NL-G-F</sup> , 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.
ChP tissue proteome was dysregulated in APP <sup>NL-G-F</sup> 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.
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.
Sujets
PID Serval
serval:BIB_AA3F1D78EAA6
PMID
Open Access
Oui
Date de création
2024-07-19T12:10:12.937Z
Date de création dans IRIS
2025-05-20T21:39:51Z
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Nom
39020361_BIB_AA3F1D78EAA6.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
4.37 MB
Format
Adobe PDF
PID Serval
serval:BIB_AA3F1D78EAA6.P001
URN
urn:nbn:ch:serval-BIB_AA3F1D78EAA61
Somme de contrôle
(MD5):d0e4e9a14f4eca32b6e9a1122edd9cee