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. How...
| Authors: | ; ; ; ; ; ; ; |
|---|---|
| Format: | Article |
| Status: | Published version |
| Publication date: | 2021 |
| Country: | España |
| Institution: | Universidad de Barcelona |
| Repository: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/180534 |
| Online Access: | https://hdl.handle.net/2445/180534 |
| Access Level: | Open access |
| Keyword: | Marcadors bioquímics Malaltia d'Alzheimer Biochemical markers Alzheimer's disease |
| _version_ | 1878733841641766912 |
|---|---|
| author | Barranco Muñoz, Neus |
| author2 | Plá, Virginia Alcolea, Daniel Sánchez-Domínguez, Irene Fischer-Colbrie, Reiner Ferrer, Isidro Lleó Bisa, Alberto Aguado, Fernando |
| author2_role | author author author author author author author |
| author_browse | Aguado, Fernando Alcolea, Daniel Barranco Muñoz, Neus Ferrer, Isidro Fischer-Colbrie, Reiner Lleó Bisa, Alberto Plá, Virginia Sánchez-Domínguez, Irene |
| author_facet | Barranco Muñoz, Neus Plá, Virginia Alcolea, Daniel Sánchez-Domínguez, Irene Fischer-Colbrie, Reiner Ferrer, Isidro Lleó Bisa, Alberto Aguado, Fernando |
| author_role | author |
| collection | Dipòsit Digital de la UB |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_5e1026741d5b2e452dfe8b4e069e9b2d |
| institution | Universidad de Barcelona |
| instname_str | Universidad de Barcelona |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:diposit.ub.edu:2445/180534 |
| publishDate | 2021 |
| publishDateSort | 2021 |
| publisher | Springer Science and Business Media LLC |
| publisherStr | Springer Science and Business Media LLC |
| reponame_str | Dipòsit Digital de la UB |
| spelling | Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer’s disease Barranco Muñoz, Neus Plá, Virginia Alcolea, Daniel Sánchez-Domínguez, Irene Fischer-Colbrie, Reiner Ferrer, Isidro Lleó Bisa, Alberto Aguado, Fernando Marcadors bioquímics Malaltia d'Alzheimer Biochemical markers 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. 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. Springer Science and Business Media LLC https://hdl.handle.net/2445/180534 |
| spellingShingle | Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer’s disease Barranco Muñoz, Neus Marcadors bioquímics Malaltia d'Alzheimer Biochemical markers Alzheimer's disease |
| status_str | publishedVersion |
| title | 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_short | 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 |
| topic | Marcadors bioquímics Malaltia d'Alzheimer Biochemical markers Alzheimer's disease |
| topic_facet | Marcadors bioquímics Malaltia d'Alzheimer Biochemical markers Alzheimer's disease |
| url | https://hdl.handle.net/2445/180534 |