9 results on '"Anna Bonaterra-Pastra"'
Search Results
2. Circulating TIMP-1 is associated with hematoma volume in patients with spontaneous intracranial hemorrhage
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Josune Orbe, José A. Páramo, Jose A. Rodriguez, Carmen Roncal, Estefanía Toledo, Roberto Muñoz-Arrondo, Anna Bonaterra-Pastra, Juan Marta-Enguita, Joan Montaner, Manuel Navarro-Oviedo, Beatriz Zandio, and Mar Hernández-Guillamon
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Male ,medicine.medical_specialty ,Neurology ,Molecular biology ,Intracranial haemorrhage ,lcsh:Medicine ,030204 cardiovascular system & hematology ,Matrix metalloproteinase ,Gastroenterology ,Severity of Illness Index ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Hematoma ,Downregulation and upregulation ,Bleeding time ,Internal medicine ,medicine ,Animals ,Humans ,In patient ,Prospective Studies ,cardiovascular diseases ,lcsh:Science ,Aged ,Aged, 80 and over ,Multidisciplinary ,Tissue Inhibitor of Metalloproteinase-1 ,medicine.diagnostic_test ,business.industry ,lcsh:R ,medicine.disease ,Disease Models, Animal ,Matrix Metalloproteinase 7 ,Biomarker (medicine) ,Female ,lcsh:Q ,business ,Tomography, X-Ray Computed ,Head ,Intracranial Hemorrhages ,030217 neurology & neurosurgery ,Biomarkers ,Neuroscience - Abstract
Matrix metalloproteinases (MMPs) are proteolytic zinc-endopeptidases regulated by tissue Inhibitors of matrix metalloproteinases (TIMPs). We evaluated the potential of MMPs and TIMPs as clinical tools for Intracranial Haemorrhage (ICH). Spontaneous non‐traumatic ICH patients were recruited from two hospitals: Complejo Hospitalario de Navarra (CHN = 29) and Vall d´Hebron (VdH = 76). Plasmatic levels of MMP-1, −2, −7, −9, −10 and TIMP-1 and their relationship with clinical, radiological and functional variables were evaluated. We further studied the effect of TIMP-1 (0.05–0.2 mg/Kg) in an experimental tail-bleeding model. In CHN, TIMP-1 was associated with admission-hematoma volume and MMP-7 was elevated in patients with deep when compared to lobar hematoma. In VdH, admission-hematoma volume was associated with TIMP-1 and MMP-7. When data from both hospitals were combined, we observed that an increase in 1 ng/ml in TIMP-1 was associated with an increase of 0.14 ml in haemorrhage (combined β = 0.14, 95% CI = 0.08–0.21). Likewise, mice receiving TIMP-1 (0.2 mg/Kg) showed a shorter bleeding time (p
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- 2020
3. MFG-E8 (LACTADHERIN): a novel marker associated with cerebral amyloid angiopathy
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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, 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, and Vall d'Hebron Barcelona Hospital Campus
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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 - Abstract
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.
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- 2021
4. Granulovacuolar degeneration bodies are neuron-selective lysosomal structures induced by intracellular tau pathology
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Markus Tolnay, Wiep Scheper, Sonia Vazquez-Sanchez, Florence Clavaguera, René J. P. Musters, Jeroen J.M. Hoozemans, Anna Nölle, Matthijs Verhage, Anna Maria van Ziel, Ernesto Berenjeno-Correa, Anna Bonaterra-Pastra, Jan R.T. van Weering, Vera I. Wiersma, Vrije Universiteit Amsterdam [Amsterdam] (VU), Vrije Universiteit Medical Centre (VUMC), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University Hospital Basel [Basel], Academic Medical Center, Gestionnaire, Hal Sorbonne Université, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Functional Genomics, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Human genetics, Pathology, Physiology, and AII - Inflammatory diseases
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Male ,0301 basic medicine ,Tau pathology ,[SDV]Life Sciences [q-bio] ,Endocytic cycle ,Granulovacuolar degeneration bodies ,Mice, Transgenic ,tau Proteins ,Vacuole ,Pathology and Forensic Medicine ,Green fluorescent protein ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Lysosome ,medicine ,Animals ,Humans ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Cells, Cultured ,Aged ,Aged, 80 and over ,Neurons ,Original Paper ,LAMP1 ,Chemistry ,Brain ,Human brain ,Casein kinase 1 δ ,3. Good health ,Cell biology ,Mice, Inbred C57BL ,[SDV] Life Sciences [q-bio] ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Tauopathies ,Astrocytes ,Vacuoles ,Female ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Neurology (clinical) ,Neuron ,Lysosomes ,030217 neurology & neurosurgery ,Intracellular ,Drugs, Chinese Herbal - Abstract
Granulovacuolar degeneration bodies (GVBs) are membrane-bound vacuolar structures harboring a dense core that accumulate in the brains of patients with neurodegenerative disorders, including Alzheimer’s disease and other tauopathies. Insight into the origin of GVBs and their connection to tau pathology has been limited by the lack of suitable experimental models for GVB formation. Here, we used confocal, automated, super-resolution and electron microscopy to demonstrate that the seeding of tau pathology triggers the formation of GVBs in different mouse models in vivo and in primary mouse neurons in vitro. Seeding-induced intracellular tau aggregation, but not seed exposure alone, causes GVB formation in cultured neurons, but not in astrocytes. The extent of tau pathology strongly correlates with the GVB load. Tau-induced GVBs are immunoreactive for the established GVB markers CK1δ, CK1ɛ, CHMP2B, pPERK, peIF2α and pIRE1α and contain a LAMP1- and LIMP2-positive single membrane that surrounds the dense core and vacuole. The proteolysis reporter DQ-BSA is detected in the majority of GVBs, demonstrating that GVBs contain degraded endocytic cargo. GFP-tagged CK1δ accumulates in the GVB core, whereas GFP-tagged tau or GFP alone does not, indicating selective targeting of cytosolic proteins to GVBs. Taken together, we established the first in vitro model for GVB formation by seeding tau pathology in primary neurons. The tau-induced GVBs have the marker signature and morphological characteristics of GVBs in the human brain. We show that GVBs are lysosomal structures distinguished by the accumulation of a characteristic subset of proteins in a dense core. Electronic supplementary material The online version of this article (10.1007/s00401-019-02046-4) contains supplementary material, which is available to authorized users.
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- 2019
5. Comparison of Plasma Lipoprotein Composition and Function in Cerebral Amyloid Angiopathy and Alzheimer’s Disease
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David Rodriguez-Luna, Soledad Pérez-Sánchez, Pere Cardona Portela, Joan Montaner, Olalla Pancorbo, Rocío Vera, Silvia Tur, Maria Del Mar Freijo, Anna Bonaterra-Pastra, José Luis Sánchez-Quesada, Andrea Rivas-Urbina, Lucia Lebrato-Hernández, Juan F. Arenillas, Núria Puig, Sofia Fernández-de-Retana, Maite Martínez-Zabaleta, Sonia Benitez, Mar Hernández-Guillamon, Francesc Pujadas, Institut Català de la Salut, [Bonaterra-Pastra A, Fernández-de-Retana S, Hernández-Guillamon M] Laboratori de recerca neurovascular, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Rivas-Urbina A, Puig N, Benítez S] Cardiovascular Biochemistry Group, Research Institute of the Hospital de Sant Pau (IIB Sant Pau), Barcelona, Spain. [Pancorbo O, Rodríguez-Luna D] Grup de Recerca en Ictus, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Pujadas F] Unitat de Demència, Servei de Neurologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Montaner J] Laboratori de recerca neurovascular, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Stroke Unit, Virgen del Rocío University Hospital, Sevilla, Spain. Department of Neurology, Virgen Macarena University Hospital, Sevilla, Spain. Stroke Research Program, Institute of Biomedicine of Sevilla, IBiS, Sevilla, Spain, and Vall d'Hebron Barcelona Hospital Campus
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0301 basic medicine ,Apolipoprotein E ,Very low-density lipoprotein ,Lipoproteïnes ,Medicine (miscellaneous) ,Proteinas ,Amino Acids, Peptides, and Proteins::Proteins::Lipoproteins [CHEMICALS AND DRUGS] ,0302 clinical medicine ,Alzheimer, Enfermedad de ,Senile plaques ,lcsh:QH301-705.5 ,Nervous System Diseases::Central Nervous System Diseases::Brain Diseases [DISEASES] ,Otros calificadores::Otros calificadores::/metabolismo [Otros calificadores] ,medicine.diagnostic_test ,Lípidos ,Other subheadings::Other subheadings::/metabolism [Other subheadings] ,Amyloidosis ,Alzheimer's disease ,Lipids ,Lipoproteïnes de la sang - Metabolisme ,Lipid profile ,lipid profile ,Neurology ,Cervell - Malalties ,aminoácidos, péptidos y proteínas::proteínas::lipoproteínas [COMPUESTOS QUÍMICOS Y DROGAS] ,3207.11 Neuropatología ,lipids (amino acids, peptides, and proteins) ,Cerebral amyloid angiopathy ,Alzheimer’s disease ,medicine.medical_specialty ,Lipoproteins ,Article ,General Biochemistry, Genetics and Molecular Biology ,s disease ,03 medical and health sciences ,Lipoprotein composition ,Internal medicine ,Parenchyma ,mental disorders ,medicine ,cardiovascular diseases ,Cerebro - Enfermedades ,Alzheimer’ ,cerebral amyloid angiopathy ,Intracerebral hemorrhage ,enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales [ENFERMEDADES] ,business.industry ,lipoprotein composition ,Proteins ,nutritional and metabolic diseases ,medicine.disease ,030104 developmental biology ,Endocrinology ,Malaltia d'Alzheimer ,Apolipoproteins ,lcsh:Biology (General) ,Amiloïdosi ,business ,apolipoproteins ,030217 neurology & neurosurgery ,Lipoprotein - Abstract
Producción Científica, Cerebral amyloid angiopathy (CAA) refers to beta-amyloid (Aβ) deposition in brain vessels and is clinically the main cause of lobar intracerebral hemorrhage (ICH). Aβ can also accumulate in brain parenchyma forming neuritic plaques in Alzheimer’s disease (AD). Our study aimed to determine whether the peripheral lipid profile and lipoprotein composition are associated with cerebral beta-amyloidosis pathology and may reflect biological differences in AD and CAA. For this purpose, lipid and apolipoproteins levels were analyzed in plasma from 51 ICH-CAA patients (collected during the chronic phase of the disease), 60 AD patients, and 60 control subjects. Lipoproteins (VLDL, LDL, and HDL) were isolated and their composition and pro/antioxidant ability were determined. We observed that alterations in the lipid profile and lipoprotein composition were remarkable in the ICH-CAA group compared to control subjects, whereas the AD group presented no specific alterations compared with controls. ICH-CAA patients presented an atheroprotective profile, which consisted of lower total and LDL cholesterol levels. Plasma from chronic ICH-CAA patients also showed a redistribution of ApoC-III from HDL to VLDL and a higher ApoE/ApoC-III ratio in HDL. Whether these alterations reflect a protective response or have a causative effect on the pathology requires further investigation., Instituto de Salud Carlos III y Fondo Europeo de Desarrollo Regional (FEDER) - (grant PI13/00364, PI16/00471, PI14/01134 and PI17/00275), Instituto de Salud Carlos III - (grant FI17/00031), Instituto de Salud Carlos III, Programa Miguel Servet - (grant CPII17/00010), Instituto de Salud Carlos III - (project RD16/0019/0021), Generalitat de Catalunya - (Grupo 2017-SGR-1149)
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- 2021
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6. Association of CD2AP neuronal deposits with Braak neurofibrillary stage in Alzheimer’s disease
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Alberto Rábano, Anna Bonaterra-Pastra, Mar Hernández-Guillamon, Elena Martínez-Sáez, Jessica Camacho, Teresa Moliné, Paula Marazuela, Garazi Serna, Santiago Ramón y Cajal, Institut Català de la Salut, [Camacho J, Ramón Y Cajal S, Martínez-Sáez E] Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Ciències Morfològiques, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Rábano A] Neuropathology Department, CIEN Foundation, Alzheimer’s Centre Queen Sofía Foundation, Madrid, Spain. [Marazuela P, Bonaterra-Pastra A, Hernández-Guillamon M] Laboratori de Recerca Neurovascular, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Serna G] Departament de Ciències Morfològiques, Universitat Autònoma de Barcelona, Bellaterra, Spain. Molecular Oncology Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Moliné T] Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Pathology ,medicine.medical_specialty ,Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Genome-Wide Association Study [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,tau Proteins ,Neurones ,CD2AP ,Biology ,Pick's disease ,Pathology and Forensic Medicine ,Progressive supranuclear palsy ,Tangle ,Alzheimer Disease ,medicine ,Neuropil ,Corticobasal degeneration ,Humans ,tau ,Phosphorylation ,Research Articles ,Nervous System::Neurons::Neurofibrils::Neurofibrillary Tangles [ANATOMY] ,Neurons ,enfermedades del sistema nervioso::enfermedades del sistema nervioso::enfermedades neurodegenerativas::taupatías::enfermedad de Alzheimer [ENFERMEDADES] ,General Neuroscience ,tauopathies ,Neurofibrillary Tangles ,Human brain ,Alzheimer's disease ,medicine.disease ,Cortex (botany) ,Nervous System Diseases::Nervous System Diseases::Neurodegenerative Diseases::Tauopathies::Alzheimer Disease [DISEASES] ,Alzheimer, Malaltia d' ,Genòmica ,medicine.anatomical_structure ,técnicas de investigación::métodos epidemiológicos::diseño de la investigación epidemiológica::estudio de asociación genómica completa [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Immunohistochemistry ,Neurology (clinical) ,Supranuclear Palsy, Progressive ,sistema nervioso::neuronas::neurofibrillas::ovillos neurofibrilares [ANATOMÍA] ,Genome-Wide Association Study ,Research Article - Abstract
Alzheimer; CD2AP; Enfermedad de Pick Alzheimer's disease; CD2AP; Pick's disease Alzheimer; CD2AP; Malaltia de Pick Genome-wide association studies have described several genes as genetic susceptibility loci for Alzheimer's disease (AD). Among them, CD2AP encodes CD2-associated protein, a scaffold protein implicated in dynamic actin remodeling and membrane trafficking during endocytosis and cytokinesis. Although a clear link between CD2AP defects and glomerular pathology has been described, little is known about the function of CD2AP in the brain. The aim of this study was to analyze the distribution of CD2AP in the AD brain and its potential associations with tau aggregation and β-amyloid (Aβ) deposition. First, we performed immunohistochemical analysis of CD2AP expression in brain tissue from AD patients and controls (N = 60). Our results showed granular CD2AP immunoreactivity in the human brain endothelium in all samples. In AD cases, no CD2AP was found to be associated with Aβ deposits in vessels or parenchymal plaques. CD2AP neuronal inclusions similar to neurofibrillary tangles (NFT) and neuropil thread-like deposits were found only in AD samples. Moreover, immunofluorescence analysis revealed that CD2AP colocalized with pTau. Regarding CD2AP neuronal distribution, a hierarchical progression from the entorhinal to the temporal and occipital cortex was detected. We found that CD2AP immunodetection in neurons was strongly and positively associated with Braak neurofibrillary stage, independent of age and other pathological hallmarks. To further investigate the association between pTau and CD2AP, we included samples from cases of primary tauopathies (corticobasal degeneration [CBD], progressive supranuclear palsy [PSP], and Pick's disease [PiD]) in our study. Among these cases, CD2AP positivity was only found in PiD samples as neurofibrillary tangle-like and Pick body-like deposits, whereas no neuronal CD2AP deposits were detected in PSP or CBD samples, which suggested an association of CD2AP neuronal expression with 3R-Tau-diseases. In conclusion, our findings open a new road to investigate the complex cellular mechanism underlying the tangle conformation and tau pathology in the brain. This work was funded by Instituto de Salud Carlos III (ISCIII) (PI17/00275, PI20/00465), cofinanced by the European Regional Development Fund (FEDER). The Neurovascular Research Laboratory is part of the INVICTUS+ network, ISCIII, Spain (RD16/0019/0021). M.H.-G. is supported by the Miguel Servet Programme, ISCIII, Spain (CPII17/00010)
- Published
- 2021
7. Neuron‐selective induction of granulovacuolar degeneration bodies: A lysosomal stress response to tau aggregation?
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Sonia Vazquez-Sanchez, Wiep Scheper, Anna Nolle, Florence Clavaguera, Ernesto Berenjeno-Correa, Anna Bonaterra-Pastra, Jeroen J.M. Hoozemans, Matthijs Verhage, Jan R.T. van Weering, Vera I. Wiersma, and Marieke van Ziel
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Granulovacuolar degeneration ,Epidemiology ,Chemistry ,Health Policy ,Cell biology ,Fight-or-flight response ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,medicine.anatomical_structure ,Developmental Neuroscience ,medicine ,Neurology (clinical) ,Neuron ,Geriatrics and Gerontology - Published
- 2020
8. Impact of Cerebral Amyloid Angiopathy in Two Transgenic Mouse Models of Cerebral β-Amyloidosis: A Neuropathological Study
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Berta Paez, Paula Marazuela, Anna Bonaterra Pastra, Maria Mar Hernandez Guillamon, Montse Solé, Institut Català de la Salut, Laboratori de Recerca Neurovascular, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Mice, Transgenic ,Plaque, Amyloid ,enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::enfermedades arteriales intracraneales::enfermedades arteriales cerebrales::angiopatía amiloide cerebral [ENFERMEDADES] ,Catalysis ,Inorganic Chemistry ,Mice ,Alzheimer Disease ,Animals ,Amino Acids, Peptides, and Proteins::Peptides::Amyloid beta-Peptides [CHEMICALS AND DRUGS] ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy ,Amyloid beta-Peptides ,Organic Chemistry ,Brain ,Amyloidosis ,General Medicine ,Eukaryota::animales::grupos de población animal::animales modificados genéticamente::ratones transgénicos [ORGANISMOS] ,APP23 ,5xFAD ,cerebral β-amyloidosis ,preclinical MRI ,cerebral microbleeds ,Computer Science Applications ,Cerebral Amyloid Angiopathy ,Disease Models, Animal ,Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Intracranial Arterial Diseases::Cerebral Arterial Diseases::Cerebral Amyloid Angiopathy [DISEASES] ,Amiloïdosi ,aminoácidos, péptidos y proteínas::péptidos::péptidos beta amiloides [COMPUESTOS QUÍMICOS Y DROGAS] ,Female ,Ratolins transgènics ,Malalties cerebrovasculars ,Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, Transgenic [ORGANISMS] - Abstract
Microhemorragias cerebrales; Beta-amiloidosis cerebral; Resonancia magnética preclínica Cerebral microbleeds; Cerebral beta-amyloidosis; Preclinical MRI Microhemorràgies cerebrals; Beta-amiloidosi cerebral; Ressonància magnètica preclínica The pathological accumulation of parenchymal and vascular amyloid-beta (Aβ) are the main hallmarks of Alzheimer’s disease (AD) and Cerebral Amyloid Angiopathy (CAA), respectively. Emerging evidence raises an important contribution of vascular dysfunction in AD pathology that could partially explain the failure of anti-Aβ therapies in this field. Transgenic mice models of cerebral β-amyloidosis are essential to a better understanding of the mechanisms underlying amyloid accumulation in the cerebrovasculature and its interactions with neuritic plaque deposition. Here, our main objective was to evaluate the progression of both parenchymal and vascular deposition in APP23 and 5xFAD transgenic mice in relation to age and sex. We first showed a significant age-dependent accumulation of extracellular Aβ deposits in both transgenic models, with a greater increase in APP23 females. We confirmed that CAA pathology was more prominent in the APP23 mice, demonstrating a higher progression of Aβ-positive vessels with age, but not linked to sex, and detecting a pronounced burden of cerebral microbleeds (cMBs) by magnetic resonance imaging (MRI). In contrast, 5xFAD mice did not present CAA, as shown by the negligible Aβ presence in cerebral vessels and the occurrence of occasional cMBs comparable to WT mice. In conclusion, the APP23 mouse model is an interesting tool to study the overlap between vascular and parenchymal Aβ deposition and to evaluate future disease-modifying therapy before its translation to the clinic. This work was funded by the Instituto de Salud Carlos III (ISCIII), (PI20/00465) and co-financed by the European Regional Development Fund (FEDER). The Neurovascular Research Laboratory is part of the RICORS-ICTUS-Enfermedades Vasculares Cerebrales network, ISCIII, Spain (RD21/0006/0007).
- Published
- 2022
9. Brain ApoA-I, ApoJ and ApoE Immunodetection in Cerebral Amyloid Angiopathy
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Jessica Camacho, Santiago Ramón y Cajal, Elena Martínez-Sáez, Anna Bonaterra-Pastra, Teresa Moliné, Mar Hernández-Guillamon, Institut Català de la Salut, [Camacho J, Moliné T, Ramón Y Cajal S, Martínez-Sáez E] Servei d’Anatomia Patològica, Hospital Universitari Vall d'Hebron, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Bonaterra-Pastra A, Hernández-Guillamon M] Laboratori de recerca en malalties neurovasculars, Vall d’Hebron Institut de Recerca, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain., and Vall d'Hebron Barcelona Hospital Campus
- Subjects
0301 basic medicine ,Apolipoprotein E ,lípidos::lipoproteínas::apolipoproteínas::apolipoproteínas A::apolipoproteína A-I [COMPUESTOS QUÍMICOS Y DROGAS] ,Pathology ,medicine.medical_specialty ,clusterin ,enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::enfermedades arteriales intracraneales::enfermedades arteriales cerebrales::angiopatía amiloide cerebral [ENFERMEDADES] ,Autopsy ,Lipids::Lipoproteins::Apolipoproteins::Apolipoproteins E [CHEMICALS AND DRUGS] ,lcsh:RC346-429 ,03 medical and health sciences ,0302 clinical medicine ,Other subheadings::Other subheadings::/immunology [Other subheadings] ,Lipids::Lipoproteins::Apolipoproteins::Apolipoproteins A::Apolipoprotein A-I [CHEMICALS AND DRUGS] ,Vasos sanguinis - Malalties - Aspectes immunològics ,Parenchyma ,mental disorders ,medicine ,lípidos::lipoproteínas::apolipoproteínas::apolipoproteínas E [COMPUESTOS QUÍMICOS Y DROGAS] ,Otros calificadores::Otros calificadores::/inmunología [Otros calificadores] ,cardiovascular diseases ,Pathological ,cerebral amyloid angiopathy ,lcsh:Neurology. Diseases of the nervous system ,Cause of death ,Original Research ,Intracerebral hemorrhage ,ApoJ ,Clusterin ,biology ,business.industry ,β-amyloid ,ApoA-I ,nutritional and metabolic diseases ,medicine.disease ,intracerebral hemorrhage ,Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Intracranial Arterial Diseases::Cerebral Arterial Diseases::Cerebral Amyloid Angiopathy [DISEASES] ,030104 developmental biology ,Neurology ,Apolipoproteïnes ,biology.protein ,Cervell - Malalties - Aspectes immunològics ,lipids (amino acids, peptides, and proteins) ,Neurology (clinical) ,Cerebral amyloid angiopathy ,business ,030217 neurology & neurosurgery ,ApoE - Abstract
ApoA-I; ApoE; Cerebral amyloid angiopathy ApoA-I; ApoE; Angiopatía amiloide cerebral ApoA-I; ApoE; Angiopatia amiloide cerebral Cerebral amyloid angiopathy (CAA) is a common cause of lobar intracerebral hemorrhage (ICH) in elderly individuals and it is the result of the cerebrovascular deposition of beta-amyloid (Aβ) protein. CAA is frequently found in patients with Alzheimer's disease (AD), although it has an independent contribution to the cognitive deterioration associated with age. Specific apolipoproteins (Apo) have been associated with Aβ fibrillization and clearance from the brain. In this regard, in the present study, we analyzed the brain levels of ApoE, ApoA-I, and ApoJ/clusterin in autopsy brains from 20 post-mortem cases with CAA type I, CAA type II, with parenchymal Aβ deposits or without Aβ deposits. Our objective was to find a possible differential pattern of apolipoproteins distribution in the brain depending on the CAA pathological presentation. The protein expression levels were adjusted by the APOE genotype of the patients included in the study. We found that ApoE and ApoJ were abundantly present in meningeal, cortical, and capillary vessels of the brains with vascular Aβ accumulation. ApoE and ApoJ also deposited extracellularly in the parenchyma, especially in cases presenting Aβ diffuse and neuritic parenchymal deposits. In contrast, ApoA-I staining was only relevant in capillary walls in CAA type I cases. On the other hand, ICH was the principal cause of death among CAA patients in our cohort. We found that CAA patients with ICH more commonly had APOEε2 compared with CAA patients without ICH. In addition, patients who suffered an ICH presented higher vascular ApoE levels in brain. However, higher ApoE presence in cortical arteries was the only independent predictor of suffering an ICH in our cohort after adjusting by age and APOE genotype. In conclusion, while ApoE and ApoJ appear to be involved in both vascular and parenchymal Aβ pathology, ApoA-I seems to be mainly associated with CAA, especially in CAA type I pathology. We consider that our study helps to molecularly characterize the distribution subtypes of Aβ deposition within the brain.
- Published
- 2019
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