Llorens, Franc

[["dc.bibliographiccitation.firstpage","461"],["dc.bibliographiccitation.journal","Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring"],["dc.bibliographiccitation.lastpage","470"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Kruse, Niels"],["dc.contributor.author","Heslegrave, Amanda"],["dc.contributor.author","Gupta, Vandana"],["dc.contributor.author","Foiani, Martha"],["dc.contributor.author","Villar-Piqué, Anna"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Lehmann, Sylvain"],["dc.contributor.author","Teunissen, Charlotte"],["dc.contributor.author","Blennow, Kaj"],["dc.contributor.author","Zetterberg, Henrik"],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Zerr, Inga"],["dc.contributor.author","Llorens, Franc"],["dc.date.accessioned","2019-07-09T11:49:35Z"],["dc.date.available","2019-07-09T11:49:35Z"],["dc.date.issued","2018"],["dc.description.abstract","ntroduction: Cerebrospinal fluid α-synuclein level is increased in sporadic Creutzfeldt-Jakob disease cases. However, the clinical value of this biomarker remains to be established. In this study, we have addressed the clinical validation parameters and the interlaboratory reproducibility by using an electrochemiluminescent assay. Methods: Cerebrospinal fluid α-synuclein was quantified in a total of 188 sporadic Creutzfeldt-Jakob disease and non-Creutzfeldt-Jakob-disease cases to determine sensitivity and specificity values and lot-to-lot variability. Two round robin tests with 70 additional cases were performed in six independent laboratories. Results: A sensitivity of 93% and a specificity of 96% were achieved in discriminating sporadic Creutzfeldt-Jakob disease. No differences were detected between lots. The mean interlaboratory coefficient of variation was 23%, and the intralaboratory coefficient of variations ranged 2.70%-11.39%. Overall, 97% of samples were correctly diagnosed. Discussion: The herein validated α-synuclein assay is robust, accurate, and reproducible in identifying Creutzfeldt-Jakob disease cases. Thus, it is ready for implementation in the clinical practice to support the diagnosis of Creutzfeldt-Jakob disease."],["dc.identifier.doi","10.1016/j.dadm.2018.06.005"],["dc.identifier.pmid","30294658"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15718"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59586"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.subject.ddc","610"],["dc.title","Interlaboratory validation of cerebrospinal fluid α-synuclein quantification in the diagnosis of sporadic Creutzfeldt-Jakob disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","83"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Molecular Neurodegeneration"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Llorens, Franc"],["dc.contributor.author","Thüne, 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","Andréoletti, 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-Valle, Raquel"],["dc.contributor.author","Ferrer, Isidro"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2019-07-09T11:44:59Z"],["dc.date.available","2019-07-09T11:44:59Z"],["dc.date.issued","2017"],["dc.description.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."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.1186/s13024-017-0226-4"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14995"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59135"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.intern","In goescholar not merged with http://resolver.sub.uni-goettingen.de/purl?gs-1/15151 but duplicate"],["dc.rights","CC BY 4.0"],["dc.rights.access","openAccess"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","YKL-40 in the brain and cerebrospinal fluid of neurodegenerative dementias"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","89"],["dc.bibliographiccitation.journal","Frontiers in neurology"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Garcia-Esparcia, Paula"],["dc.contributor.author","López-González, Irene"],["dc.contributor.author","Grau-Rivera, Oriol"],["dc.contributor.author","García-Garrido, María Francisca"],["dc.contributor.author","Konetti, Anusha"],["dc.contributor.author","Llorens, Franc"],["dc.contributor.author","Zafar, Saima"],["dc.contributor.author","Carmona, Margarita"],["dc.contributor.author","Del Rio, José Antonio"],["dc.contributor.author","Zerr, Inga"],["dc.contributor.author","Gelpi, Ellen"],["dc.contributor.author","Ferrer, Isidro"],["dc.date.accessioned","2019-07-09T11:44:52Z"],["dc.date.available","2019-07-09T11:44:52Z"],["dc.date.issued","2017"],["dc.description.abstract","OBJECTIVES: The goal of this study was to assess mitochondrial function, energy, and purine metabolism, protein synthesis machinery from the nucleolus to the ribosome, inflammation, and expression of newly identified ectopic olfactory receptors (ORs) and taste receptors (TASRs) in the frontal cortex of typical cases of dementia with Lewy bodies (DLB) and cases with rapid clinical course (rpDLB: 2 years or less) compared with middle-aged non-affected individuals, in order to learn about the biochemical abnormalities underlying Lewy body pathology. METHODS: Real-time quantitative PCR, mitochondrial enzymatic assays, and analysis of β-amyloid, tau, and synuclein species were used. RESULTS: The main alterations in DLB and rpDLB, which are more marked in the rapidly progressive forms, include (i) deregulated expression of several mRNAs and proteins of mitochondrial subunits, and reduced activity of complexes I, II, III, and IV of the mitochondrial respiratory chain; (ii) reduced expression of selected molecules involved in energy metabolism and increased expression of enzymes involved in purine metabolism; (iii) abnormal expression of nucleolar proteins, rRNA18S, genes encoding ribosomal proteins, and initiation factors of the transcription at the ribosome; (iv) discrete inflammation; and (v) marked deregulation of brain ORs and TASRs, respectively. Severe mitochondrial dysfunction involving activity of four complexes, minimal inflammatory responses, and dramatic altered expression of ORs and TASRs discriminate DLB from Alzheimer's disease. Altered solubility and aggregation of α-synuclein, increased β-amyloid bound to membranes, and absence of soluble tau oligomers are common in DLB and rpDLB. Low levels of soluble β-amyloid are found in DLB. However, increased soluble β-amyloid 1-40 and β-amyloid 1-42, and increased TNFα mRNA and protein expression, distinguish rpDLB. CONCLUSION: Molecular alterations in frontal cortex in DLB involve key biochemical pathways such as mitochondria and energy metabolism, protein synthesis, purine metabolism, among others and are accompanied by discrete innate inflammatory response."],["dc.identifier.doi","10.3389/fneur.2017.00089"],["dc.identifier.pmid","28348546"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14942"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59117"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1664-2295"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Dementia with Lewy Bodies: Molecular Pathology in the Frontal Cortex in Typical and Rapidly Progressive Forms."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","220"],["dc.bibliographiccitation.journal","Frontiers in Aging Neuroscience"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Kanata, Eirini"],["dc.contributor.author","Thüne, Katrin"],["dc.contributor.author","Xanthopoulos, Konstantinos"],["dc.contributor.author","Ferrer, Isidre"],["dc.contributor.author","Dafou, Dimitra"],["dc.contributor.author","Zerr, Inga"],["dc.contributor.author","Sklaviadis, Theodoros"],["dc.contributor.author","Llorens, Franc"],["dc.date.accessioned","2019-07-09T11:45:43Z"],["dc.date.available","2019-07-09T11:45:43Z"],["dc.date.issued","2018"],["dc.description.abstract","Prion diseases are transmissible progressive neurodegenerative conditions characterized by rapid neuronal loss accompanied by a heterogeneous neuropathology, including spongiform degeneration, gliosis and protein aggregation. The pathogenic mechanisms and the origins of prion diseases remain unclear on the molecular level. Even though neurodegenerative diseases, including prion diseases, represent distinct entities, their pathogenesis shares a number of features including disturbed protein homeostasis, an overload of protein clearance pathways, the aggregation of pathological altered proteins, and the dysfunction and/or loss of specific neuronal populations. Recently, direct links have been established between neurodegenerative diseases and miRNA dysregulated patterns. miRNAs are a class of small non-coding RNAs involved in the fundamental post-transcriptional regulation of gene expression. Studies of miRNA alterations in the brain and body fluids in human prion diseases provide important insights into potential miRNA-associated disease mechanisms and biomarker candidates. miRNA alterations in prion disease models represent a unique tool to investigate the cause-consequence relationships of miRNA dysregulation in prion disease pathology, and to evaluate the use of miRNAs in diagnosis as biomarkers. Here, we provide an overview of studies on miRNA alterations in human prion diseases and relevant disease models, in relation to pertinent studies on other neurodegenerative diseases."],["dc.identifier.doi","10.3389/fnagi.2018.00220"],["dc.identifier.pmid","30083102"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15293"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59293"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1663-4365"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","MicroRNA Alterations in the Brain and Body Fluids of Humans and Animal Prion Disease Models: Current Status and Perspectives"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]