YKL-40 in the brain and cerebrospinal fluid of neurodegenerative dementias
| Autor: | 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 |
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| Přispěvatelé: | Universitat de Barcelona, Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), university medical school, Partenaires INRAE, German Center for Neurodegenerative Diseases, Aristotle University of Thessaloniki, San Raffaele Scientific Institute, Research Institute, Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centro de Investigacion en Sanidad Animal (INIA-CISA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria = National Institute for Agricultural and Food Research and Technology (INIA), Institute of Neuropathology, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Institut d'Investigacions Biomèdiques August Pi i Sunyer |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
musculoskeletal diseases YKL-40 Médecine humaine et pathologie Mice Transgenic lcsh:Geriatrics metabolism [Neurodegenerative Diseases] lcsh:RC346-429 metabolism [Cerebrospinal Fluid] Mice Neuroinflammation ddc:570 mental disorders Animals Humans metabolism [Dementia] Chitinase-3-Like Protein 1 lcsh:Neurology. Diseases of the nervous system Glycoproteins Aged Brain Cerebrospinal fluid Chitinase 3-like 1 Neurodegenerative dementias biosynthesis [Chitinase-3-Like Protein 1] Malalties neurodegeneratives Neurodegenerative diseases Microbiology and Parasitology CHI3L1 protein human Neurodegenerative Diseases Middle Aged Microbiologie et Parasitologie lcsh:RC952-954.6 [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology metabolism [Brain] analysis [Chitinase-3-Like Protein 1] Dementia Female Human health and pathology analysis [Biomarkers] [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology Biomarkers Research Article Glicoproteïnes |
| Zdroj: | Molecular Neurodegeneration 1 (12), 83. (2017) Molecular neurodegeneration 12(1), 83 (2017). doi:10.1186/s13024-017-0226-4 Recercat. Dipósit de la Recerca de Catalunya instname Molecular Neurodegeneration Molecular Neurodegeneration, BioMed Central, 2017, 12 (1), pp.83. ⟨10.1186/s13024-017-0226-4⟩ Molecular Neurodegeneration, Vol 12, Iss 1, Pp 1-21 (2017) Repositorio de Resultados de Investigación del INIA INIA: Repositorio de Resultados de Investigación del INIA Dipòsit Digital de la UB Universidad de Barcelona Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria INIA |
| ISSN: | 1750-1326 |
| Popis: | 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 0.05, 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. |
| Databáze: | OpenAIRE |
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