Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer’s disease
Abstract 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...
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| Format: | Article |
| Language: | English |
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BMC
2021-09-01
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| Series: | Translational Neurodegeneration |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40035-021-00263-0 |
| _version_ | 1819067644020523008 |
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| author | Neus Barranco Virginia Plá Daniel Alcolea Irene Sánchez-Domínguez Reiner Fischer-Colbrie Isidro Ferrer Alberto Lleó Fernando Aguado |
| author_facet | Neus Barranco Virginia Plá Daniel Alcolea Irene Sánchez-Domínguez Reiner Fischer-Colbrie Isidro Ferrer Alberto Lleó Fernando Aguado |
| author_sort | Neus Barranco |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-21T16:21:31Z |
| format | Article |
| id | doaj.art-b1799d7ef6e440089c5948eebb165e0c |
| institution | Directory Open Access Journal |
| issn | 2047-9158 |
| language | English |
| last_indexed | 2024-12-21T16:21:31Z |
| publishDate | 2021-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Translational Neurodegeneration |
| spelling | doaj.art-b1799d7ef6e440089c5948eebb165e0c2022-12-21T18:57:33ZengBMCTranslational Neurodegeneration2047-91582021-09-0110111510.1186/s40035-021-00263-0Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer’s diseaseNeus Barranco0Virginia Plá1Daniel Alcolea2Irene Sánchez-Domínguez3Reiner Fischer-Colbrie4Isidro Ferrer5Alberto Lleó6Fernando Aguado7Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of BarcelonaDepartment of Cell Biology, Physiology and Immunology, Faculty of Biology, University of BarcelonaMemory Unit, Department of Neurology, Sant Pau Biomedical Research Institute. Sant Pau Hospital, Autonomous University of BarcelonaDepartment of Cell Biology, Physiology and Immunology, Faculty of Biology, University of BarcelonaDepartment of Pharmacology, Innsbruck Medical UniversityInstitute of Neurosciences, University of BarcelonaMemory Unit, Department of Neurology, Sant Pau Biomedical Research Institute. Sant Pau Hospital, Autonomous University of BarcelonaDepartment of Cell Biology, Physiology and Immunology, Faculty of Biology, University of BarcelonaAbstract 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.https://doi.org/10.1186/s40035-021-00263-0Alzheimer’s diseaseBiomarkersCerebral cortexCerebrospinal fluidGranulovacuolar degenerationPCSK1 |
| spellingShingle | Neus Barranco Virginia Plá Daniel Alcolea Irene Sánchez-Domínguez Reiner Fischer-Colbrie Isidro Ferrer Alberto Lleó Fernando Aguado Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer’s disease Translational Neurodegeneration Alzheimer’s disease Biomarkers Cerebral cortex Cerebrospinal fluid Granulovacuolar degeneration PCSK1 |
| 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 | Alzheimer’s disease Biomarkers Cerebral cortex Cerebrospinal fluid Granulovacuolar degeneration PCSK1 |
| url | https://doi.org/10.1186/s40035-021-00263-0 |
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