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 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.

Bibliographic Details

Main Authors:	Llorens, F., Thüne, K., Tahir, W., Kanata, E., Diaz-Lucena, D., Xanthopoulos, K., Kovatsi, E., Pleschka, C., Garcia-Esparcia, P., Schmitz, M., Ozbay, D., Correia, S., Correia, Â, Milosevic, I., Andréoletti, O., Fernández-Borges, N., Vorberg, I. M., Glatzel, M., Sklaviadis, T., Torres, J. M., Krasemann, S., Sánchez-Valle, R., Ferrer, I., Zerr, I.
Format:	artículo biblioteca
Language:	English
Published:	BioMed Central 2017
Subjects:	Chitinase 3-like 1, YKL-40, Neuroinflammation, Cerebrospinal fluid, Neurodegenerative dementias, Brain,
Online Access:	http://hdl.handle.net/20.500.12792/2398 http://hdl.handle.net/10261/292391
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