MFG-E8 (LACTADHERIN): a novel marker associated with cerebral amyloid angiopathy
Malaltia d'Alzheimer; Biomarcadors; Microdissecció de captura làser
| Autores: | , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:11351/7436 |
| Acceso en línea: | https://hdl.handle.net/11351/7436 http://hdl.handle.net/11351/7436 |
| Access Level: | acceso abierto |
| Palabra clave: | Malalties cerebrovasculars - Patogènesi Pèptids - Metabolisme DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Intracranial Arterial Diseases::Cerebral Arterial Diseases::Cerebral Amyloid Angiopathy Other subheadings::Other subheadings::Other subheadings::/pathology CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Peptides::Amyloid beta-Peptides Other subheadings::Other subheadings::Other subheadings::/metabolism ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::enfermedades arteriales intracraneales::enfermedades arteriales cerebrales::angiopatía amiloide cerebral Otros calificadores::Otros calificadores::Otros calificadores::/patología COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::péptidos::péptidos beta amiloides Otros calificadores::Otros calificadores::Otros calificadores::/metabolismo |
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MFG-E8 (LACTADHERIN): a novel marker associated with cerebral amyloid angiopathy |
| title |
MFG-E8 (LACTADHERIN): a novel marker associated with cerebral amyloid angiopathy |
| spellingShingle |
MFG-E8 (LACTADHERIN): a novel marker associated with cerebral amyloid angiopathy Marazuela Fuentes, Paula Malalties cerebrovasculars - Patogènesi Pèptids - Metabolisme DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Intracranial Arterial Diseases::Cerebral Arterial Diseases::Cerebral Amyloid Angiopathy Other subheadings::Other subheadings::Other subheadings::/pathology CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Peptides::Amyloid beta-Peptides Other subheadings::Other subheadings::Other subheadings::/metabolism ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::enfermedades arteriales intracraneales::enfermedades arteriales cerebrales::angiopatía amiloide cerebral Otros calificadores::Otros calificadores::Otros calificadores::/patología COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::péptidos::péptidos beta amiloides Otros calificadores::Otros calificadores::Otros calificadores::/metabolismo |
| title_short |
MFG-E8 (LACTADHERIN): a novel marker associated with cerebral amyloid angiopathy |
| title_full |
MFG-E8 (LACTADHERIN): a novel marker associated with cerebral amyloid angiopathy |
| title_fullStr |
MFG-E8 (LACTADHERIN): a novel marker associated with cerebral amyloid angiopathy |
| title_full_unstemmed |
MFG-E8 (LACTADHERIN): a novel marker associated with cerebral amyloid angiopathy |
| title_sort |
MFG-E8 (LACTADHERIN): a novel marker associated with cerebral amyloid angiopathy |
| dc.creator.none.fl_str_mv |
Marazuela Fuentes, Paula Solé Piñol, Montserrat Bonaterra Pastra, Anna Pizarro Gonzálvez, Jesús Camacho Soriano, Jessica Martinez Saez, Elena Antima Castillo Ribelles, Laura Pancorbo Rosal, Olalla Rodriguez Luna, David Pujadas Navinés, Francesc Delgado Martínez, Maria Pilar Hernandez Guillamon, Maria Mar |
| author |
Marazuela Fuentes, Paula |
| author_facet |
Marazuela Fuentes, Paula Solé Piñol, Montserrat Bonaterra Pastra, Anna Pizarro Gonzálvez, Jesús Camacho Soriano, Jessica Martinez Saez, Elena Antima Castillo Ribelles, Laura Pancorbo Rosal, Olalla Rodriguez Luna, David Pujadas Navinés, Francesc Delgado Martínez, Maria Pilar Hernandez Guillamon, Maria Mar |
| author_role |
author |
| author2 |
Solé Piñol, Montserrat Bonaterra Pastra, Anna Pizarro Gonzálvez, Jesús Camacho Soriano, Jessica Martinez Saez, Elena Antima Castillo Ribelles, Laura Pancorbo Rosal, Olalla Rodriguez Luna, David Pujadas Navinés, Francesc Delgado Martínez, Maria Pilar Hernandez Guillamon, Maria Mar |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Institut Català de la Salut [Marazuela P, Solé M, Bonaterra-Pastra A, Pizarro J, Delgado P, Hernández-Guillamon M] Laboratori de Recerca Neurovascular, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Camacho J, Martínez-Sáez E] Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Castillo-Ribelles L] Servei de Bioquímica Clínica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Pancorbo O, Rodríguez-Luna D] Unitat d’Ictus, Servei de Neurologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Pujadas F] Servei de Neurologia, Unitat de Demència, Vall d’Hebron Hospital Universitari, Barcelona, Spain Vall d'Hebron Barcelona Hospital Campus |
| dc.subject.none.fl_str_mv |
Malalties cerebrovasculars - Patogènesi Pèptids - Metabolisme DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Intracranial Arterial Diseases::Cerebral Arterial Diseases::Cerebral Amyloid Angiopathy Other subheadings::Other subheadings::Other subheadings::/pathology CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Peptides::Amyloid beta-Peptides Other subheadings::Other subheadings::Other subheadings::/metabolism ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::enfermedades arteriales intracraneales::enfermedades arteriales cerebrales::angiopatía amiloide cerebral Otros calificadores::Otros calificadores::Otros calificadores::/patología COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::péptidos::péptidos beta amiloides Otros calificadores::Otros calificadores::Otros calificadores::/metabolismo |
| topic |
Malalties cerebrovasculars - Patogènesi Pèptids - Metabolisme DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Intracranial Arterial Diseases::Cerebral Arterial Diseases::Cerebral Amyloid Angiopathy Other subheadings::Other subheadings::Other subheadings::/pathology CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Peptides::Amyloid beta-Peptides Other subheadings::Other subheadings::Other subheadings::/metabolism ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::enfermedades arteriales intracraneales::enfermedades arteriales cerebrales::angiopatía amiloide cerebral Otros calificadores::Otros calificadores::Otros calificadores::/patología COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::péptidos::péptidos beta amiloides Otros calificadores::Otros calificadores::Otros calificadores::/metabolismo |
| description |
Malaltia d'Alzheimer; Biomarcadors; Microdissecció de captura làser |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021 2022 2022 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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https://hdl.handle.net/11351/7436 http://hdl.handle.net/11351/7436 |
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https://hdl.handle.net/11351/7436 http://hdl.handle.net/11351/7436 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
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Acta Neuropathologica Communications;9 https://doi.org/10.1186/s40478-021-01257-9 info:eu-repo/grantAgreement/ES/PE2017-2020/PI20%2F00465 info:eu-repo/grantAgreement/ES/PE2013-2016/RD16%2F0019%2F0021 |
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Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
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Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf |
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BMC |
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Scientia reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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MFG-E8 (LACTADHERIN): a novel marker associated with cerebral amyloid angiopathyMarazuela Fuentes, PaulaSolé Piñol, MontserratBonaterra Pastra, AnnaPizarro Gonzálvez, JesúsCamacho Soriano, JessicaMartinez Saez, Elena AntimaCastillo Ribelles, LauraPancorbo Rosal, OlallaRodriguez Luna, DavidPujadas Navinés, FrancescDelgado Martínez, Maria PilarHernandez Guillamon, Maria MarMalalties cerebrovasculars - PatogènesiPèptids - MetabolismeDISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Intracranial Arterial Diseases::Cerebral Arterial Diseases::Cerebral Amyloid AngiopathyOther subheadings::Other subheadings::Other subheadings::/pathologyCHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Peptides::Amyloid beta-PeptidesOther subheadings::Other subheadings::Other subheadings::/metabolismENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::enfermedades arteriales intracraneales::enfermedades arteriales cerebrales::angiopatía amiloide cerebralOtros calificadores::Otros calificadores::Otros calificadores::/patologíaCOMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::péptidos::péptidos beta amiloidesOtros calificadores::Otros calificadores::Otros calificadores::/metabolismoMalaltia d'Alzheimer; Biomarcadors; Microdissecció de captura làserAlzheimer's disease; Biomarkers; Laser capture microdissectionEnfermedad de Alzheimer; Biomarcadores; Microdisección por captura láserBrain accumulation of amyloid-beta (Aβ) is a crucial feature in Alzheimer´s disease (AD) and cerebral amyloid angiopathy (CAA), although the pathophysiological relationship between these diseases remains unclear. Numerous proteins are associated with Aβ deposited in parenchymal plaques and/or cerebral vessels. We hypothesized that the study of these proteins would increase our understanding of the overlap and biological differences between these two pathologies and may yield new diagnostic tools and specific therapeutic targets. We used a laser capture microdissection approach combined with mass spectrometry in the APP23 transgenic mouse model of cerebral-β-amyloidosis to specifically identify vascular Aβ-associated proteins. We focused on one of the main proteins detected in the Aβ-affected cerebrovasculature: MFG-E8 (milk fat globule-EGF factor 8), also known as lactadherin. We first validated the presence of MFG-E8 in mouse and human brains. Immunofluorescence and immunoblotting studies revealed that MFG-E8 brain levels were higher in APP23 mice than in WT mice. Furthermore, MFG-E8 was strongly detected in Aβ-positive vessels in human postmortem CAA brains, whereas MFG-E8 was not present in parenchymal Aβ deposits. Levels of MFG-E8 were additionally analysed in serum and cerebrospinal fluid (CSF) from patients diagnosed with CAA, patients with AD and control subjects. Whereas no differences were found in MFG-E8 serum levels between groups, MFG-E8 concentration was significantly lower in the CSF of CAA patients compared to controls and AD patients. Finally, in human vascular smooth muscle cells MFG-E8 was protective against the toxic effects of the treatment with the Aβ40 peptide containing the Dutch mutation. In summary, our study shows that MFG-E8 is highly associated with CAA pathology and highlights MFG-E8 as a new CSF biomarker that could potentially be used to differentiate cerebrovascular Aβ pathology from parenchymal Aβ deposition.This work was funded by the Instituto de Salud Carlos III (ISCIII), (PI20/00465), co-financed by the European Regional Development Fund (FEDER). The Neurovascular Research Laboratory is part of the INVICTUS + network, ISCIII, Spain (RD16/0019/0021). P.M. held a predoctoral fellowship from the Vall d’Hebron Research Institute. MMV is supported by the BIONIC project (no. 733050822, which has been made possible by ZonMW as part of ‘Memorabel’, the research and innovation program for dementia, as part of the Dutch national ‘Deltaplan for Dementia’:the CAFÉ project (the National Institutes of Health, USA, grant number 5R01NS104147-02), and a grant from the Selfridges Group Foundation (NR170024). The BIONIC project is a consortium of Radboudumc, LUMC, ADX Neurosciences, and Rhode Island University.BMCInstitut Català de la Salut[Marazuela P, Solé M, Bonaterra-Pastra A, Pizarro J, Delgado P, Hernández-Guillamon M] Laboratori de Recerca Neurovascular, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Camacho J, Martínez-Sáez E] Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Castillo-Ribelles L] Servei de Bioquímica Clínica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Pancorbo O, Rodríguez-Luna D] Unitat d’Ictus, Servei de Neurologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Pujadas F] Servei de Neurologia, Unitat de Demència, Vall d’Hebron Hospital Universitari, Barcelona, SpainVall d'Hebron Barcelona Hospital Campus202220222021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttps://hdl.handle.net/11351/7436http://hdl.handle.net/11351/7436Scientiareponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésActa Neuropathologica Communications;9https://doi.org/10.1186/s40478-021-01257-9info:eu-repo/grantAgreement/ES/PE2017-2020/PI20%2F00465info:eu-repo/grantAgreement/ES/PE2013-2016/RD16%2F0019%2F0021Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:11351/74362026-05-29T05:05:01Z |
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