Importance of extracellular vesicle secretion at the blood-cerebrospinal fluid interface in the pathogenesis of Alzheimer's disease.
2021
Аутори:
Vandendriessche, CharysseBalusu, Sriram
Van Cauwenberghe, Caroline
Brkić, Marjana
Pauwels, Marie
Plehiers, Nele
Bruggeman, Arnout
Dujardin, Pieter
Van Imschoot, Griet
Van Wonterghem, Elien
Hendrix, An
Baeke, Femke
De Rycke, Riet
Gevaert, Kris
Vandenbroucke, Roosmarijn E.
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
Increasing evidence indicates that extracellular vesicles (EVs) play an important role in the pathogenesis of Alzheimer's disease (AD). We previously reported that the blood-cerebrospinal fluid (CSF) interface, formed by the choroid plexus epithelial (CPE) cells, releases an increased amount of EVs into the CSF in response to peripheral inflammation. Here, we studied the importance of CP-mediated EV release in AD pathogenesis. We observed increased EV levels in the CSF of young transgenic APP/PS1 mice which correlated with high amyloid beta (Aβ) CSF levels at this age. The intracerebroventricular (icv) injection of Aβ oligomers (AβO) in wild-type mice revealed a significant increase of EVs in the CSF, signifying that the presence of CSF-AβO is sufficient to induce increased EV secretion. Using in vivo, in vitro and ex vivo approaches, we identified the CP as a major source of the CSF-EVs. Interestingly, AβO-induced, CP-derived EVs induced pro-inflammatory effects in mixed cortical cultures. Proteome analysis of these EVs revealed the presence of several pro-inflammatory proteins, including the complement protein C3. Strikingly, inhibition of EV production using GW4869 resulted in protection against acute AβO-induced cognitive decline. Further research into the underlying mechanisms of this EV secretion might open up novel therapeutic strategies to impact the pathogenesis and progression of AD.
Кључне речи:
Alzheimer’s disease; Blood–cerebrospinal fluid barrier; Choroid plexus; Complement; Extracellular vesiclesИзвор:
Acta Neuropathologica Communications, 2021, 9, 1, 143-Финансирање / пројекти:
- European Cooperation in Science and Technology (COST) BM1402
- Belgian Federal Science Policy Office IAP-VI-18
- Foundation for Alzheimer's Research (SAO-FRA)
- FWO
DOI: 10.1186/s40478-021-01245-z
ISSN: 2051-5960
PubMed: 34425919
WoS: 000687665400001
Scopus: 2-s2.0-85113749627
URI
https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-021-01245-zhttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC8381545
https://radar.ibiss.bg.ac.rs/handle/123456789/4476