2026-04-14T07:05:21Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1242202025-12-04T19:25:02Zcom_2072_1057col_2072_478858col_2072_478916col_2072_478917col_2072_478929

00925njm 22002777a 4500 dc Llorens Torres, Franc author Thune, Katrin author Tahir, Waqas author Kanata, Eirini author Diaz-Lucena, Daniela author Xanthopoulos, Konstantinos author Kovatsi, Eleni author Pleschka, Catharina author Garcia Esparcia, Paula author Schmitz, Matthias author Ozbay, Duru author Correia, Susana author Correia, Ângela author Milosevic, Ira author Andreoletti, Olivier author Fernández Borges, Natalia author Vorberg, Ina M. author Glatzel, Markus author Sklaviadis, Theodoros author Torres, Juan Maria author Krasemann, Susanne author Sánchez del Valle Díaz, Raquel author Ferrer, Isidro (Ferrer Abizanda) author Zerr, Inga author 2018-09-03T13:17:32Z 2018-09-03T13:17:32Z 2017-11-10 2018-07-24T11:55:57Z 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. Malalties neurodegeneratives Glicoproteïnes Neurodegenerative Diseases Glycoproteins Ykl-40 in the brain and cerebrospinal fluid of neurodegenerative dementias