TY  - JOUR
AU  - Vandendriessche, Charysse
AU  - Balusu, Sriram
AU  - Van Cauwenberghe, Caroline
AU  - Brkić, Marjana
AU  - Pauwels, Marie
AU  - Plehiers, Nele
AU  - Bruggeman, Arnout
AU  - Dujardin, Pieter
AU  - Van Imschoot, Griet
AU  - Van Wonterghem, Elien
AU  - Hendrix, An
AU  - Baeke, Femke
AU  - De Rycke, Riet
AU  - Gevaert, Kris
AU  - Vandenbroucke, Roosmarijn E.
PY  - 2021
UR  - https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-021-01245-z
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC8381545
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4476
AB  - 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.
T2  - Acta Neuropathologica Communications
T1  - Importance of extracellular vesicle secretion at the blood-cerebrospinal fluid interface in the pathogenesis of Alzheimer's disease.
IS  - 1
VL  - 9
DO  - 10.1186/s40478-021-01245-z
SP  - 143
ER  - 

@article{
author = "Vandendriessche, Charysse and Balusu, Sriram and Van Cauwenberghe, Caroline and Brkić, Marjana and Pauwels, Marie and Plehiers, Nele and Bruggeman, Arnout and Dujardin, Pieter and Van Imschoot, Griet and Van Wonterghem, Elien and Hendrix, An and Baeke, Femke and De Rycke, Riet and Gevaert, Kris and Vandenbroucke, Roosmarijn E.",
year = "2021",
abstract = "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.",
journal = "Acta Neuropathologica Communications",
title = "Importance of extracellular vesicle secretion at the blood-cerebrospinal fluid interface in the pathogenesis of Alzheimer's disease.",
number = "1",
volume = "9",
doi = "10.1186/s40478-021-01245-z",
pages = "143"
}

Vandendriessche, C., Balusu, S., Van Cauwenberghe, C., Brkić, M., Pauwels, M., Plehiers, N., Bruggeman, A., Dujardin, P., Van Imschoot, G., Van Wonterghem, E., Hendrix, A., Baeke, F., De Rycke, R., Gevaert, K.,& Vandenbroucke, R. E.. (2021). Importance of extracellular vesicle secretion at the blood-cerebrospinal fluid interface in the pathogenesis of Alzheimer's disease.. in Acta Neuropathologica Communications, 9(1), 143.
https://doi.org/10.1186/s40478-021-01245-z

Vandendriessche C, Balusu S, Van Cauwenberghe C, Brkić M, Pauwels M, Plehiers N, Bruggeman A, Dujardin P, Van Imschoot G, Van Wonterghem E, Hendrix A, Baeke F, De Rycke R, Gevaert K, Vandenbroucke RE. Importance of extracellular vesicle secretion at the blood-cerebrospinal fluid interface in the pathogenesis of Alzheimer's disease.. in Acta Neuropathologica Communications. 2021;9(1):143.
doi:10.1186/s40478-021-01245-z .

Vandendriessche, Charysse, Balusu, 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., "Importance of extracellular vesicle secretion at the blood-cerebrospinal fluid interface in the pathogenesis of Alzheimer's disease." in Acta Neuropathologica Communications, 9, no. 1 (2021):143,
https://doi.org/10.1186/s40478-021-01245-z . .

TY  - JOUR
AU  - Balusu, Sriram
AU  - Van Wonterghem, Elien
AU  - De Rycke, Riet
AU  - Raemdonck, Koen
AU  - Stremersch, Stephan
AU  - Gevaert, Kris
AU  - Brkić, Marjana
AU  - Demeestere, Delphine
AU  - Vanhooren, Valerie
AU  - Hendrix, An
AU  - Libert, Claude
AU  - Vandenbroucke, Roosmarijn E.
PY  - 2016
UR  - http://embomolmed.embopress.org/lookup/doi/10.15252/emmm.201606271
UR  - https://www.scopus.com/record/display.uri?eid=2-s2.0-84989915450&origin=SingleRecordEmailAlert&txGid=66B9A38F509F4540CF41E07DD21FB6C0.wsnAw8kcdt7IPYLO0V48gA:27#
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2471
AB  - Here, we identified release of extracellular vesicles (EVs) by the choroid plexus epithelium (CPE) as a new mechanism of blood–brain communication. Systemic inflammation induced an increase in EVs and associated pro-inflammatory miRNAs, including miR-146a and miR-155, in the CSF. Interestingly, this was associated with an increase in amount of multivesicular bodies (MVBs) and exosomes per MVB in the CPE cells. Additionally, we could mimic this using LPS-stimulated primary CPE cells and choroid plexus explants. These choroid plexus-derived EVs can enter the brain parenchyma and are taken up by astrocytes and microglia, inducing miRNA target repression and inflammatory gene up-regulation. Interestingly, this could be blocked in vivo by intracerebroventricular (icv) injection of an inhibitor of exosome production. Our data show that CPE cells sense and transmit information about the peripheral inflammatory status to the central nervous system (CNS) via the release of EVs into the CSF, which transfer this pro-inflammatory message to recipient brain cells. Additionally, we revealed that blockage of EV secretion decreases brain inflammation, which opens up new avenues to treat systemic inflammatory diseases such as sepsis.
PB  - Blackwell Publishing Ltd
T2  - EMBO Molecular Medicine
T1  - Identification of a novel mechanism of blood–brain communication during peripheral inflammation via choroid plexus‐derived extracellular vesicles
IS  - 10
VL  - 8
DO  - 10.15252/emmm.201606271
SP  - 1162
EP  - 1183
ER  - 

@article{
author = "Balusu, Sriram and Van Wonterghem, Elien and De Rycke, Riet and Raemdonck, Koen and Stremersch, Stephan and Gevaert, Kris and Brkić, Marjana and Demeestere, Delphine and Vanhooren, Valerie and Hendrix, An and Libert, Claude and Vandenbroucke, Roosmarijn E.",
year = "2016",
abstract = "Here, we identified release of extracellular vesicles (EVs) by the choroid plexus epithelium (CPE) as a new mechanism of blood–brain communication. Systemic inflammation induced an increase in EVs and associated pro-inflammatory miRNAs, including miR-146a and miR-155, in the CSF. Interestingly, this was associated with an increase in amount of multivesicular bodies (MVBs) and exosomes per MVB in the CPE cells. Additionally, we could mimic this using LPS-stimulated primary CPE cells and choroid plexus explants. These choroid plexus-derived EVs can enter the brain parenchyma and are taken up by astrocytes and microglia, inducing miRNA target repression and inflammatory gene up-regulation. Interestingly, this could be blocked in vivo by intracerebroventricular (icv) injection of an inhibitor of exosome production. Our data show that CPE cells sense and transmit information about the peripheral inflammatory status to the central nervous system (CNS) via the release of EVs into the CSF, which transfer this pro-inflammatory message to recipient brain cells. Additionally, we revealed that blockage of EV secretion decreases brain inflammation, which opens up new avenues to treat systemic inflammatory diseases such as sepsis.",
publisher = "Blackwell Publishing Ltd",
journal = "EMBO Molecular Medicine",
title = "Identification of a novel mechanism of blood–brain communication during peripheral inflammation via choroid plexus‐derived extracellular vesicles",
number = "10",
volume = "8",
doi = "10.15252/emmm.201606271",
pages = "1162-1183"
}

Balusu, S., Van Wonterghem, E., De Rycke, R., Raemdonck, K., Stremersch, S., Gevaert, K., Brkić, M., Demeestere, D., Vanhooren, V., Hendrix, A., Libert, C.,& Vandenbroucke, R. E.. (2016). Identification of a novel mechanism of blood–brain communication during peripheral inflammation via choroid plexus‐derived extracellular vesicles. in EMBO Molecular Medicine
Blackwell Publishing Ltd., 8(10), 1162-1183.
https://doi.org/10.15252/emmm.201606271

Balusu S, Van Wonterghem E, De Rycke R, Raemdonck K, Stremersch S, Gevaert K, Brkić M, Demeestere D, Vanhooren V, Hendrix A, Libert C, Vandenbroucke RE. Identification of a novel mechanism of blood–brain communication during peripheral inflammation via choroid plexus‐derived extracellular vesicles. in EMBO Molecular Medicine. 2016;8(10):1162-1183.
doi:10.15252/emmm.201606271 .

Balusu, Sriram, Van Wonterghem, Elien, De Rycke, Riet, Raemdonck, Koen, Stremersch, Stephan, Gevaert, Kris, Brkić, Marjana, Demeestere, Delphine, Vanhooren, Valerie, Hendrix, An, Libert, Claude, Vandenbroucke, Roosmarijn E., "Identification of a novel mechanism of blood–brain communication during peripheral inflammation via choroid plexus‐derived extracellular vesicles" in EMBO Molecular Medicine, 8, no. 10 (2016):1162-1183,
https://doi.org/10.15252/emmm.201606271 . .