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

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dc.contributor.author	Llorens Torres, Franc
dc.contributor.author	Thune, Katrin
dc.contributor.author	Tahir, Waqas
dc.contributor.author	Kanata, Eirini
dc.contributor.author	Diaz-Lucena, Daniela
dc.contributor.author	Xanthopoulos, Konstantinos
dc.contributor.author	Kovatsi, Eleni
dc.contributor.author	Pleschka, Catharina
dc.contributor.author	Garcia Esparcia, Paula
dc.contributor.author	Schmitz, Matthias
dc.contributor.author	Ozbay, Duru
dc.contributor.author	Correia, Susana
dc.contributor.author	Correia, Ângela
dc.contributor.author	Milosevic, Ira
dc.contributor.author	Andreoletti, Olivier
dc.contributor.author	Fernández Borges, Natalia
dc.contributor.author	Vorberg, Ina M.
dc.contributor.author	Glatzel, Markus
dc.contributor.author	Sklaviadis, Theodoros
dc.contributor.author	Torres, Juan Maria
dc.contributor.author	Krasemann, Susanne
dc.contributor.author	Sánchez del Valle Díaz, Raquel
dc.contributor.author	Ferrer, Isidro (Ferrer Abizanda)
dc.contributor.author	Zerr, Inga
dc.date	2018-09-03T13:17:32Z
dc.date	2018-09-03T13:17:32Z
dc.date	2017-11-10
dc.date	2018-07-24T11:55:57Z
dc.identifier	29126445
dc.identifier.uri	http://hdl.handle.net/2445/124220
dc.description	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 beta-amyloid plaques, and surrounding vessels with beta-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.
dc.format	21 p.
dc.format	application/pdf
dc.language	eng
dc.publisher	BioMed Central
dc.relation	Reproducció del document publicat a: http://dx.doi.org/10.1186/s13024-017-0226-4
dc.relation	Molecular Neurodegeneration, 2017, vol. 12, num. 83
dc.relation	http://dx.doi.org/10.1186/s13024-017-0226-4
dc.rights	cc by (c) Llorens et al., 2017
dc.rights	http://creativecommons.org/licenses/by/3.0/es/
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	Malalties neurodegeneratives
dc.subject	Glicoproteïnes
dc.subject	Neurodegenerative diseases
dc.subject	Glycoproteins
dc.title	Ykl-40 in the brain and cerebrospinal fluid of neurodegenerative dementias
dc.type	info:eu-repo/semantics/article
dc.type	info:eu-repo/semantics/publishedVersion

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

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