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YKL-40 in the brain and cerebrospinal fluid of neurodegenerative dementias

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 associ...

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Detalles Bibliográficos
Autores principales: Llorens, Franc, Thüne, 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, Andréoletti, Olivier, Fernández-Borges, Natalia, Vorberg, Ina M., Glatzel, Markus, Sklaviadis, Theodoros, Torres, Juan Maria, Krasemann, Susanne, Sánchez-Valle, Raquel, Ferrer, Isidro, Zerr, Inga
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681777/
https://www.ncbi.nlm.nih.gov/pubmed/29126445
http://dx.doi.org/10.1186/s13024-017-0226-4
Descripción
Sumario: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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13024-017-0226-4) contains supplementary material, which is available to authorized users.