Correia, Angela

[["dc.bibliographiccitation.artnumber","83"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Molecular Neurodegeneration"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Llorens, Franc"],["dc.contributor.author","Thüne, Katrin"],["dc.contributor.author","Tahir, Waqas"],["dc.contributor.author","Kanata, Eirini"],["dc.contributor.author","Diaz-Lucena, Daniela"],["dc.contributor.author","Xanthopoulos, Konstantinos"],["dc.contributor.author","Kovatsi, Eleni"],["dc.contributor.author","Pleschka, Catharina"],["dc.contributor.author","Garcia-Esparcia, Paula"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Ozbay, Duru"],["dc.contributor.author","Correia, Susana"],["dc.contributor.author","Correia, Ângela"],["dc.contributor.author","Milosevic, Ira"],["dc.contributor.author","Andréoletti, Olivier"],["dc.contributor.author","Fernández-Borges, Natalia"],["dc.contributor.author","Vorberg, Ina M."],["dc.contributor.author","Glatzel, Markus"],["dc.contributor.author","Sklaviadis, Theodoros"],["dc.contributor.author","Torres, Juan Maria"],["dc.contributor.author","Krasemann, Susanne"],["dc.contributor.author","Sánchez-Valle, Raquel"],["dc.contributor.author","Ferrer, Isidro"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2019-07-09T11:44:59Z"],["dc.date.available","2019-07-09T11:44:59Z"],["dc.date.issued","2017"],["dc.description.abstract","Background YKL-40 (also known as Chitinase 3-like 1) is a glycoprotein produced by inflammatory, cancer and stem cells. Its physiological role is not completely understood but YKL-40 is elevated in the brain and cerebrospinal fluid (CSF) in several neurological and neurodegenerative diseases associated with inflammatory processes. Yet the precise characterization of YKL-40 in dementia cases is missing. Methods In the present study, we comparatively analysed YKL-40 levels in the brain and CSF samples from neurodegenerative dementias of different aetiologies characterized by the presence of cortical pathology and disease-specific neuroinflammatory signatures. Results YKL-40 was normally expressed in fibrillar astrocytes in the white matter. Additionally YKL-40 was highly and widely expressed in reactive protoplasmic cortical and perivascular astrocytes, and fibrillar astrocytes in sporadic Creutzfeldt-Jakob disease (sCJD). Elevated YKL-40 levels were also detected in Alzheimer’s disease (AD) but not in dementia with Lewy bodies (DLB). In AD, YKL-40-positive astrocytes were commonly found in clusters, often around β-amyloid plaques, and surrounding vessels with β-amyloid angiopathy; they were also distributed randomly in the cerebral cortex and white matter. YKL-40 overexpression appeared as a pre-clinical event as demonstrated in experimental models of prion diseases and AD pathology. CSF YKL-40 levels were measured in a cohort of 288 individuals, including neurological controls (NC) and patients diagnosed with different types of dementia. Compared to NC, increased YKL-40 levels were detected in sCJD (p < 0.001, AUC = 0.92) and AD (p < 0.001, AUC = 0.77) but not in vascular dementia (VaD) (p > 0.05, AUC = 0.71) or in DLB/Parkinson’s disease dementia (PDD) (p > 0.05, AUC = 0.70). Further, two independent patient cohorts were used to validate the increased CSF YKL-40 levels in sCJD. Additionally, increased YKL-40 levels were found in genetic prion diseases associated with the PRNP-D178N (Fatal Familial Insomnia) and PRNP-E200K mutations. Conclusions Our results unequivocally demonstrate that in neurodegenerative dementias, YKL-40 is a disease-specific marker of neuroinflammation showing its highest levels in prion diseases. Therefore, YKL-40 quantification might have a potential for application in the evaluation of therapeutic intervention in dementias with a neuroinflammatory component."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.1186/s13024-017-0226-4"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14995"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59135"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.intern","In goescholar not merged with http://resolver.sub.uni-goettingen.de/purl?gs-1/15151 but duplicate"],["dc.rights","CC BY 4.0"],["dc.rights.access","openAccess"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","YKL-40 in the brain and cerebrospinal fluid of neurodegenerative dementias"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","mds.28774"],["dc.bibliographiccitation.firstpage","39"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Movement Disorders"],["dc.bibliographiccitation.lastpage","51"],["dc.bibliographiccitation.volume","37"],["dc.contributor.affiliation","Thom, Tobias; 1\r\nDepartment of Neurology\r\nUniversity Medical Center Göttingen and the German Center for Neurodegenerative Diseases\r\nGöttingen Germany"],["dc.contributor.affiliation","Fischer, Anna‐Lisa; 1\r\nDepartment of Neurology\r\nUniversity Medical Center Göttingen and the German Center for Neurodegenerative Diseases\r\nGöttingen Germany"],["dc.contributor.affiliation","Correia, Angela; 1\r\nDepartment of Neurology\r\nUniversity Medical Center Göttingen and the German Center for Neurodegenerative Diseases\r\nGöttingen Germany"],["dc.contributor.affiliation","Correia, Susana; 1\r\nDepartment of Neurology\r\nUniversity Medical Center Göttingen and the German Center for Neurodegenerative Diseases\r\nGöttingen Germany"],["dc.contributor.affiliation","Llorens, Franc; 1\r\nDepartment of Neurology\r\nUniversity Medical Center Göttingen and the German Center for Neurodegenerative Diseases\r\nGöttingen Germany"],["dc.contributor.affiliation","Pique, Anna‐Villar; 1\r\nDepartment of Neurology\r\nUniversity Medical Center Göttingen and the German Center for Neurodegenerative Diseases\r\nGöttingen Germany"],["dc.contributor.affiliation","Möbius, Wiebke; 4\r\nDepartment for Neurogenetics\r\nEM Core Unit Max Planck Institute for Experimental Medicine\r\nGöttingen Germany"],["dc.contributor.affiliation","Domingues, Renato; 5\r\nDepartment of Experimental Neurodegeneration\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Zafar, Saima; 1\r\nDepartment of Neurology\r\nUniversity Medical Center Göttingen and the German Center for Neurodegenerative Diseases\r\nGöttingen Germany"],["dc.contributor.affiliation","Stoops, Erik; 7\r\nADx NeuroSciences\r\nGhent Belgium"],["dc.contributor.affiliation","Silva, Christopher J.; 8\r\nProduce Safety & Microbiology Research Unit, Western Regional Research Center, United States Department of Agriculture\r\nAgricultural Research Service\r\nAlbany California USA"],["dc.contributor.affiliation","Fischer, Andre; 9\r\nDepartment for Epigenetics and Systems Medicine in Neurodegenerative Diseases\r\nGerman Center for Neurodegenerative Diseases\r\nGöttingen Germany"],["dc.contributor.affiliation","Outeiro, Tiago F.; 5\r\nDepartment of Experimental Neurodegeneration\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Zerr, Inga; 1\r\nDepartment of Neurology\r\nUniversity Medical Center Göttingen and the German Center for Neurodegenerative Diseases\r\nGöttingen Germany"],["dc.contributor.author","Thom, Tobias"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Fischer, Anna‐Lisa"],["dc.contributor.author","Correia, Angela"],["dc.contributor.author","Correia, Susana"],["dc.contributor.author","Llorens, Franc"],["dc.contributor.author","Pique, Anna‐Villar"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Domingues, Renato"],["dc.contributor.author","Zafar, Saima"],["dc.contributor.author","Zerr, Inga"],["dc.contributor.author","Stoops, Erik"],["dc.contributor.author","Silva, Christopher J."],["dc.contributor.author","Fischer, André"],["dc.contributor.author","Outeiro, Tiago F."],["dc.date.accessioned","2021-09-01T06:42:58Z"],["dc.date.available","2021-09-01T06:42:58Z"],["dc.date.issued","2021"],["dc.date.updated","2022-03-21T12:51:34Z"],["dc.description.abstract","Abstract Background The cellular prion protein (PrPC) is a membrane‐bound, multifunctional protein mainly expressed in neuronal tissues. Recent studies indicate that the native trafficking of PrPC can be misused to internalize misfolded amyloid beta and α‐synuclein (aSyn) oligomers. Objectives We define PrPC's role in internalizing misfolded aSyn in α‐synucleinopathies and identify further involved proteins. Methods We performed comprehensive behavioral studies on four transgenic mouse models (ThySyn and ThySynPrP00, TgM83 and TgMPrP00) at different ages. We developed PrPC‐(over)‐expressing cell models (cell line and primary cortical neurons), used confocal laser microscopy to perform colocalization studies, applied mass spectrometry to identify interactomes, and determined disassociation constants using surface plasmon resonance (SPR) spectroscopy. Results Behavioral deficits (memory, anxiety, locomotion, etc.), reduced lifespans, and higher oligomeric aSyn levels were observed in PrPC‐expressing mice (ThySyn and TgM83), but not in homologous Prnp ablated mice (ThySynPrP00 and TgMPrP00). PrPC colocalized with and facilitated aSyn (oligomeric and monomeric) internalization in our cell‐based models. Glimepiride treatment of PrPC‐overexpressing cells reduced aSyn internalization in a dose‐dependent manner. SPR analysis showed that the binding affinity of PrPC to monomeric aSyn was lower than to oligomeric aSyn. Mass spectrometry‐based proteomic studies identified clathrin in the immunoprecipitates of PrPC and aSyn. SPR was used to show that clathrin binds to recombinant PrP, but not aSyn. Experimental disruption of clathrin‐coated vesicles significantly decreased aSyn internalization. Conclusion PrPC's native trafficking can be misused to internalize misfolded aSyn through a clathrin‐based mechanism, which may facilitate the spreading of pathological aSyn. Disruption of aSyn‐PrPC binding is, therefore, an appealing therapeutic target in α‐synucleinopathies. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society"],["dc.description.sponsorship","ADDF http://dx.doi.org/10.13039/100002565"],["dc.description.sponsorship","Fondo de Investigación Sanitaria"],["dc.identifier.doi","10.1002/mds.28774"],["dc.identifier.pmid","34448510"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/89190"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/335"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/130"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-455"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation.eissn","1531-8257"],["dc.relation.issn","0885-3185"],["dc.relation.workinggroup","RG A. Fischer (Epigenetics and Systems Medicine in Neurodegenerative Diseases)"],["dc.relation.workinggroup","RG Möbius"],["dc.relation.workinggroup","RG Outeiro (Experimental Neurodegeneration)"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited."],["dc.title","Cellular Prion Protein Mediates α‐Synuclein Uptake, Localization, and Toxicity In Vitro and In Vivo"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2927"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Aging"],["dc.bibliographiccitation.lastpage","2935"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Llorens, Franc"],["dc.contributor.author","Pracht, Alexander"],["dc.contributor.author","Thom, Tobias"],["dc.contributor.author","Correia, Angela"],["dc.contributor.author","Zafar, Saima"],["dc.contributor.author","Ferrer, Isidre"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2018-11-07T10:06:08Z"],["dc.date.available","2018-11-07T10:06:08Z"],["dc.date.issued","2016"],["dc.description.abstract","The identification of reliable diagnostic biomarkers in differential diagnosis of neurodegenerative diseases is an ongoing topic. A previous two-dimensional proteomic study on cerebrospinal fluid (CSF) revealed an elevated level of an enzyme, mitochondria! malate dehydrogenase 1 (MDH1), in sporadic Creutzfeldt-Jakob disease (sCJD) patients. Here, we could demonstrate the expression of MDH1 in neurons as well as in the neuropil. Its levels are lower in sCJD brains than in control brains. An examination of CSF-MDH1 in sCJD patients by ELISA revealed a significant elevation of CSF-MDH1 levels in sCJD patients (independently from the PRNP codon 129 MV genotype or the prion protein scrapie (PrPsc) type) in comparison to controls. In combination with total tau (tau), CSF-MDH1 detection exhibited a high diagnostic accuracy for sCJD diagnosis with a sensitivity of 97.5% and a specificity of 95.6%. A correlation study of MDH1 level in CSF with other neurodegenerative marker proteins revealed a significant positive correlation between MDH1 concentration with tau, 14-3-3 and neuron specific enolase level. In conclusion, our study indicated the potential of MDH1 in combination with tau as an additional biomarker in sCJD improving diagnostic accuracy of tau markedly."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2016"],["dc.identifier.doi","10.18632/aging.101101"],["dc.identifier.isi","000390311900024"],["dc.identifier.pmid","27852982"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14094"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39032"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Impact Journals Llc"],["dc.relation.issn","1945-4589"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Regulation of human cerebrospinal fluid malate dehydrogenase 1 in sporadic Creutzfeldt-Jakob disease patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]