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dc.contributor.authorLlorens Torres, Franc-
dc.contributor.authorThune, Katrin-
dc.contributor.authorTahir, Waqas-
dc.contributor.authorKanata, Eirini-
dc.contributor.authorDiaz-Lucena, Daniela-
dc.contributor.authorXanthopoulos, Konstantinos-
dc.contributor.authorKovatsi, Eleni-
dc.contributor.authorPleschka, Catharina-
dc.contributor.authorGarcia Esparcia, Paula-
dc.contributor.authorSchmitz, Matthias-
dc.contributor.authorOzbay, Duru-
dc.contributor.authorCorreia, Susana-
dc.contributor.authorCorreia, Ângela-
dc.contributor.authorMilosevic, Ira-
dc.contributor.authorAndreoletti, Olivier-
dc.contributor.authorFernández Borges, Natalia-
dc.contributor.authorVorberg, Ina M.-
dc.contributor.authorGlatzel, Markus-
dc.contributor.authorSklaviadis, Theodoros-
dc.contributor.authorTorres, Juan Maria-
dc.contributor.authorKrasemann, Susanne-
dc.contributor.authorSánchez Valle, Raquel-
dc.contributor.authorFerrer, Isidro (Ferrer Abizanda)-
dc.contributor.authorZerr, Inga-
dc.description.abstractBackground: 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.extent21 p.-
dc.publisherBioMed Central-
dc.relation.isformatofReproducció del document publicat a:
dc.relation.ispartofMolecular Neurodegeneration, 2017, vol. 12, num. 83-
dc.rightscc by (c) Llorens et al., 2017-
dc.subject.classificationMalalties neurodegeneratives-
dc.subject.otherNeurodegenerative diseases-
dc.titleYkl-40 in the brain and cerebrospinal fluid of neurodegenerative dementias-
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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