YKL-40 in the brain and cerebrospinal fluid of neurodegenerative dementias
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YKL-40 in the brain and cerebrospinal fluid of neurodegenerative dementias. / 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.
In: MOL NEURODEGENER, Vol. 12, No. 1, 10.11.2017, p. 83.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - YKL-40 in the brain and cerebrospinal fluid of neurodegenerative dementias
AU - Llorens, Franc
AU - Thüne, Katrin
AU - Tahir, Waqas
AU - Kanata, Eirini
AU - Diaz-Lucena, Daniela
AU - Xanthopoulos, Konstantinos
AU - Kovatsi, Eleni
AU - Pleschka, Catharina
AU - Garcia-Esparcia, Paula
AU - Schmitz, Matthias
AU - Ozbay, Duru
AU - Correia, Susana
AU - Correia, Ângela
AU - Milosevic, Ira
AU - Andréoletti, Olivier
AU - Fernández-Borges, Natalia
AU - Vorberg, Ina M
AU - Glatzel, Markus
AU - Sklaviadis, Theodoros
AU - Torres, Juan Maria
AU - Krasemann, Susanne
AU - Sánchez-Valle, Raquel
AU - Ferrer, Isidro
AU - Zerr, Inga
PY - 2017/11/10
Y1 - 2017/11/10
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1186/s13024-017-0226-4
DO - 10.1186/s13024-017-0226-4
M3 - SCORING: Journal article
C2 - 29126445
VL - 12
SP - 83
JO - MOL NEURODEGENER
JF - MOL NEURODEGENER
SN - 1750-1326
IS - 1
ER -