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

• Published in: Molecular neurodegeneration Vol. 12; no. 1; pp. 83 - 21
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 10.11.2017; BioMed Central; BMC
• Subjects: Alzheimer's disease; Arthritis; Astrocytes; Biomarkers; Brain; Brain research; Cancer; Cerebral cortex; Cerebrospinal fluid; Chitinase; Chitinase 3-like 1; Creutzfeldt-Jakob disease; Dementia; Dementia disorders; Development and progression; Gene expression; Genetic aspects; Human health and pathology; Insomnia; Lewy bodies; Life Sciences; Microbiology and Parasitology; Neurodegeneration; Neurodegenerative dementias; Neurodegenerative diseases; Neuroinflammation; Neuropathology; Pathogenesis; Physiological aspects; Senile plaques; Sleep disorders; Stem cells; Stroke; Substantia alba; Vascular dementia; YKL-40; β-Amyloid; Spain; Brain; Neuroinflammation; Cerebrospinal fluid; YKL-40; Chitinase 3-like 1; Neurodegenerative dementias
• ISSN: 1750-1326; 1750-1326
• DOI: 10.1186/s13024-017-0226-4

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. 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. 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. 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.