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Título: | YKL-40 in the brain and cerebrospinal fluid of neurodegenerative dementias |
Autor: | Llorens, Franc; Thüne, Katrin; Tahir, W.; Kanata, E.; Diaz-Lucena, Daniela; Xanthopoulos, Konstantinos; Kovatsi, E.; Pleschka, C.; Garcia-Esparcia, P.; Schmitz, Matthias; Ozbay, D.; Correia, Susana; Correia, Angela; Andréoletti, Olivier; Fernández-Borges, N.; Vorberg, I. M.; Glatzel, M.; Sklaviadis, T.; Torres, J. M.; Krasemann, S.; Sánchez-Valle, Raquel; Ferrer, Isidro; Zerr, I.; Milosevic, Ira | Palabras clave: | Chitinase 3-like 1 YKL-40 Neuroinflammation Cerebrospinal fluid Neurodegenerative dementias Brain |
Fecha de publicación: | 2017 | Editor: | BioMed Central | Citación: | Molecular Neurodegeneration 12: e83 (2017) | Resumen: | 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. | URI: | http://hdl.handle.net/10261/292391 | DOI: | 10.1186/s13024-017-0226-4 | E-ISSN: | 1750-1326 |
Aparece en las colecciones: | (INIA) Artículos |
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