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http://hdl.handle.net/2445/124220
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DC Field | Value | Language |
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dc.contributor.author | Llorens Torres, Franc | - |
dc.contributor.author | Thune, 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 | Andreoletti, 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 del Valle Díaz, Raquel | - |
dc.contributor.author | Ferrer, Isidro (Ferrer Abizanda) | - |
dc.contributor.author | Zerr, Inga | - |
dc.date.accessioned | 2018-09-03T13:17:32Z | - |
dc.date.available | 2018-09-03T13:17:32Z | - |
dc.date.issued | 2017-11-10 | - |
dc.identifier.uri | http://hdl.handle.net/2445/124220 | - |
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 beta-amyloid plaques, and surrounding vessels with beta-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.format.extent | 21 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | BioMed Central | - |
dc.relation.isformatof | Reproducció del document publicat a: http://dx.doi.org/10.1186/s13024-017-0226-4 | - |
dc.relation.ispartof | Molecular Neurodegeneration, 2017, vol. 12, num. 83 | - |
dc.relation.uri | http://dx.doi.org/10.1186/s13024-017-0226-4 | - |
dc.rights | cc by (c) Llorens et al., 2017 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | - |
dc.source | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) | - |
dc.subject.classification | Malalties neurodegeneratives | - |
dc.subject.classification | Glicoproteïnes | - |
dc.subject.other | Neurodegenerative Diseases | - |
dc.subject.other | Glycoproteins | - |
dc.title | Ykl-40 in the brain and cerebrospinal fluid of neurodegenerative dementias | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.date.updated | 2018-07-24T11:55:57Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 29126445 | - |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Patologia i Terapèutica Experimental) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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