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oai:recercat.cat:2445/1242202025-12-04T19:25:02Zcom_2072_1057col_2072_478858col_2072_478916col_2072_478917col_2072_478929

urn:hdl:2445/124220 Ykl-40 in the brain and cerebrospinal fluid of neurodegenerative dementias Llorens Torres, Franc Thune, Katrin Tahir, Waqas Kanata, Eirini Diaz-Lucena, Daniela Xanthopoulos, Konstantinos Kovatsi, Eleni Pleschka, Catharina Garcia Esparcia, Paula Schmitz, Matthias Ozbay, Duru Correia, Susana Correia, Ângela Milosevic, Ira Andreoletti, Olivier Fernández Borges, Natalia Vorberg, Ina M. Glatzel, Markus Sklaviadis, Theodoros Torres, Juan Maria Krasemann, Susanne Sánchez del Valle Díaz, Raquel Ferrer, Isidro (Ferrer Abizanda) Zerr, Inga Malalties neurodegeneratives Glicoproteïnes Neurodegenerative Diseases Glycoproteins 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. 2018-09-03T13:17:32Z 2018-09-03T13:17:32Z 2017-11-10 2018-07-24T11:55:57Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Reproducció del document publicat a: http://dx.doi.org/10.1186/s13024-017-0226-4 Molecular Neurodegeneration, 2017, vol. 12, num. 83 http://dx.doi.org/10.1186/s13024-017-0226-4 cc by (c) Llorens et al., 2017 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess BioMed Central Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))