MFG-E8 (LACTADHERIN): a novel marker associated with cerebral amyloid angiopathy
| العنوان: | MFG-E8 (LACTADHERIN): a novel marker associated with cerebral amyloid angiopathy |
|---|---|
| المؤلفون: | Pilar Delgado, Laura Castillo-Ribelles, Anna M. de Kort, Marcel M. Verbeek, David Rodriguez-Luna, Jessica Camacho, Jesús Pizarro, Olalla Pancorbo, Catharina J.M. Klijn, Elena Martínez-Sáez, Anna Bonaterra-Pastra, H. Bea Kuiperij, Montse Solé, Francesc Pujadas, Mar Hernández-Guillamon, Floris H.B.M. Schreuder, Paula Marazuela |
| المساهمون: | 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 |
| المصدر: | Acta Neuropathologica Communications Acta Neuropathologica Communications, 9 Scientia Acta Neuropathologica Communications, 9, 1 Acta Neuropathologica Communications, Vol 9, Iss 1, Pp 1-17 (2021) |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, Pathology, Vascular smooth muscle, enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::enfermedades arteriales intracraneales::enfermedades arteriales cerebrales::angiopatía amiloide cerebral [ENFERMEDADES], Mice, Cerebrospinal fluid, Medicine, Amino Acids, Peptides, and Proteins::Peptides::Amyloid beta-Peptides [CHEMICALS AND DRUGS], Cells, Cultured, Otros calificadores::Otros calificadores::/metabolismo [Otros calificadores], Laser capture microdissection, medicine.diagnostic_test, Brain, Other subheadings::Other subheadings::/metabolism [Other subheadings], Middle Aged, Alzheimer's disease, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Milk Proteins, Pathophysiology, Other subheadings::Other subheadings::/pathology [Other subheadings], Antigens, Surface, Female, Cerebral amyloid angiopathy, Otros calificadores::Otros calificadores::/patología [Otros calificadores], Genetically modified mouse, medicine.medical_specialty, Mice, Transgenic, MFG-E8, Immunofluorescence, Pathology and Forensic Medicine, Cellular and Molecular Neuroscience, All institutes and research themes of the Radboud University Medical Center, Animals, Humans, RC346-429, Aged, Lactadherin, business.industry, Research, Malalties cerebrovasculars - Patogènesi, Pèptids - Metabolisme, medicine.disease, Mice, Inbred C57BL, Cerebral Amyloid Angiopathy, Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Intracranial Arterial Diseases::Cerebral Arterial Diseases::Cerebral Amyloid Angiopathy [DISEASES], aminoácidos, péptidos y proteínas::péptidos::péptidos beta amiloides [COMPUESTOS QUÍMICOS Y DROGAS], Neurology. Diseases of the nervous system, Neurology (clinical), business, Biomarkers |
| الوصف: | Malaltia d'Alzheimer; Biomarcadors; Microdissecció de captura làser Alzheimer's disease; Biomarkers; Laser capture microdissection Enfermedad de Alzheimer; Biomarcadores; Microdisección por captura láser Brain 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. |
| وصف الملف: | application/pdf |
| تدمد: | 2051-5960 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d10560cc73d88b9e464ec7f6c9097245Test https://doi.org/10.1186/s40478-021-01257-9Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d10560cc73d88b9e464ec7f6c9097245 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20515960 |
|---|