Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer's disease

Background: New fluid biomarkers for Alzheimer's disease (AD) that reveal synaptic and neural network dysfunctions are needed for clinical practice and therapeutic trial design. Dense core vesicle (DCV) cargos are promising cerebrospinal fluid (CSF) indicators of synaptic failure in AD patients...

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Autores: Barranco Muñoz, Neus, Plá, Virginia, Alcolea, Daniel, Sánchez Domínguez, Irene, Fischer-Colbrie, Reiner, Ferrer, Isidro (Ferrer Abizanda), Lleó Bisa, Alberto, Aguado Tomàs, Fernando
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/226557
Acesso em linha:https://hdl.handle.net/2445/226557
Access Level:acceso abierto
Palavra-chave:Malaltia d'Alzheimer
Escorça cerebral
Líquid cefalorraquidi
Alzheimer's disease
Cerebral cortex
Cerebrospinal fluid
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spelling Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer's diseaseBarranco Muñoz, NeusPlá, VirginiaAlcolea, DanielSánchez Domínguez, IreneFischer-Colbrie, ReinerFerrer, Isidro (Ferrer Abizanda)Lleó Bisa, AlbertoAguado Tomàs, FernandoMalaltia d'AlzheimerEscorça cerebralLíquid cefalorraquidiAlzheimer's diseaseCerebral cortexCerebrospinal fluidBackground: New fluid biomarkers for Alzheimer's disease (AD) that reveal synaptic and neural network dysfunctions are needed for clinical practice and therapeutic trial design. Dense core vesicle (DCV) cargos are promising cerebrospinal fluid (CSF) indicators of synaptic failure in AD patients. However, their value as biomarkers has not yet been determined. Methods: Immunoassays were performed to analyze the secretory proteins prohormone convertases PC1/3 and PC2, carboxypeptidase E (CPE), secretogranins SgIII and SgII, and Cystatin C in the cerebral cortex (n = 45, provided by Bellvitge University Hospital) and CSF samples (n = 66, provided by The Sant Pau Initiative on Neurodegeneration cohort) from AD patients (n = 56) and age-matched controls (n = 55). Results: In AD tissues, most DCV proteins were aberrantly accumulated in dystrophic neurites and activated astrocytes, whereas PC1/3, PC2 and CPE were also specifically accumulated in hippocampal granulovacuolar degeneration bodies. AD individuals displayed an overall decline of secretory proteins in the CSF. Interestingly, in AD patients, the CSF levels of prohormone convertases strongly correlated inversely with those of neurodegeneration markers and directly with cognitive impairment status. Conclusions: These results demonstrate marked alterations of neuronal-specific prohormone convertases in CSF and cortical tissues of AD patients. The neuronal DCV cargos are biomarker candidates for synaptic dysfunction and neurodegeneration in AD.BioMed Central2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/226557Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1186/s40035-021-00263-0Translational Neurodegeneration, 2021, vol. 10, num.1, p. 1-15https://doi.org/10.1186/s40035-021-00263-0cc-by (c) Barranco, N. et al., 2021http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2265572026-05-27T06:46:51Z
dc.title.none.fl_str_mv Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer's disease
title Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer's disease
spellingShingle Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer's disease
Barranco Muñoz, Neus
Malaltia d'Alzheimer
Escorça cerebral
Líquid cefalorraquidi
Alzheimer's disease
Cerebral cortex
Cerebrospinal fluid
title_short Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer's disease
title_full Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer's disease
title_fullStr Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer's disease
title_full_unstemmed Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer's disease
title_sort Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer's disease
dc.creator.none.fl_str_mv Barranco Muñoz, Neus
Plá, Virginia
Alcolea, Daniel
Sánchez Domínguez, Irene
Fischer-Colbrie, Reiner
Ferrer, Isidro (Ferrer Abizanda)
Lleó Bisa, Alberto
Aguado Tomàs, Fernando
author Barranco Muñoz, Neus
author_facet Barranco Muñoz, Neus
Plá, Virginia
Alcolea, Daniel
Sánchez Domínguez, Irene
Fischer-Colbrie, Reiner
Ferrer, Isidro (Ferrer Abizanda)
Lleó Bisa, Alberto
Aguado Tomàs, Fernando
author_role author
author2 Plá, Virginia
Alcolea, Daniel
Sánchez Domínguez, Irene
Fischer-Colbrie, Reiner
Ferrer, Isidro (Ferrer Abizanda)
Lleó Bisa, Alberto
Aguado Tomàs, Fernando
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Malaltia d'Alzheimer
Escorça cerebral
Líquid cefalorraquidi
Alzheimer's disease
Cerebral cortex
Cerebrospinal fluid
topic Malaltia d'Alzheimer
Escorça cerebral
Líquid cefalorraquidi
Alzheimer's disease
Cerebral cortex
Cerebrospinal fluid
description Background: New fluid biomarkers for Alzheimer's disease (AD) that reveal synaptic and neural network dysfunctions are needed for clinical practice and therapeutic trial design. Dense core vesicle (DCV) cargos are promising cerebrospinal fluid (CSF) indicators of synaptic failure in AD patients. However, their value as biomarkers has not yet been determined. Methods: Immunoassays were performed to analyze the secretory proteins prohormone convertases PC1/3 and PC2, carboxypeptidase E (CPE), secretogranins SgIII and SgII, and Cystatin C in the cerebral cortex (n = 45, provided by Bellvitge University Hospital) and CSF samples (n = 66, provided by The Sant Pau Initiative on Neurodegeneration cohort) from AD patients (n = 56) and age-matched controls (n = 55). Results: In AD tissues, most DCV proteins were aberrantly accumulated in dystrophic neurites and activated astrocytes, whereas PC1/3, PC2 and CPE were also specifically accumulated in hippocampal granulovacuolar degeneration bodies. AD individuals displayed an overall decline of secretory proteins in the CSF. Interestingly, in AD patients, the CSF levels of prohormone convertases strongly correlated inversely with those of neurodegeneration markers and directly with cognitive impairment status. Conclusions: These results demonstrate marked alterations of neuronal-specific prohormone convertases in CSF and cortical tissues of AD patients. The neuronal DCV cargos are biomarker candidates for synaptic dysfunction and neurodegeneration in AD.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/226557
url https://hdl.handle.net/2445/226557
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/s40035-021-00263-0
Translational Neurodegeneration, 2021, vol. 10, num.1, p. 1-15
https://doi.org/10.1186/s40035-021-00263-0
dc.rights.none.fl_str_mv cc-by (c) Barranco, N. et al., 2021
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Barranco, N. et al., 2021
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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