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Mol Neurodegener. 2017 Nov 10;12(1):83. doi: 10.1186/s13024-017-0226-4.

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

Author information

1
Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Institute Carlos III, Ministry of Health, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain. franc.llorens@gmail.com.
2
Department of Neurology, University Medical School, Göttingen, Germany. franc.llorens@gmail.com.
3
Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Institute Carlos III, Ministry of Health, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
4
German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
5
Department of Neurology, University Medical School, Göttingen, Germany.
6
Laboratory of Pharmacology, School of Health Sciences, Department of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, Greece.
7
Present address: Unit of Lymphoid Malignancies, Division of Experimental Oncology, San Raffaele Scientific Institute, Milan, Italy.
8
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
9
Bellvitge University Hospital-IDIBELL, Department of Pathology and Experimental Therapeutics, University of Barcelona, Hospitalet de Llobregat, Spain.
10
European Neuroscience Institute, Göttingen, Germany.
11
Institut National de la Recherche Agronomique/Ecole Nationale Vétérinaire, Toulouse, France.
12
Centro de Investigación en Sanidad Animal (CISA-INIA), Madrid, Spain.
13
Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
14
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Abstract

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.

KEYWORDS:

Brain; Cerebrospinal fluid; Chitinase 3-like 1; Neurodegenerative dementias; Neuroinflammation; YKL-40

PMID:
29126445
PMCID:
PMC5681777
DOI:
10.1186/s13024-017-0226-4
[Indexed for MEDLINE]
Free PMC Article

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