Kruse, Niels

[["dc.bibliographiccitation.firstpage","126"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","138"],["dc.bibliographiccitation.volume","149"],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Bowman, Frederick DuBois"],["dc.contributor.author","Drake, Daniel"],["dc.contributor.author","Duong, Jimmy"],["dc.contributor.author","Blennow, Kaj"],["dc.contributor.author","El‐Agnaf, Omar"],["dc.contributor.author","Shaw, Leslie M."],["dc.contributor.author","Masucci, Jennifer"],["dc.contributor.author","Taylor, Peggy"],["dc.contributor.author","Umek, Robert M."],["dc.contributor.author","Dunty, Jill M."],["dc.contributor.author","Smith, Chris L."],["dc.contributor.author","Stoops, Erik"],["dc.contributor.author","Vanderstichele, Hugo"],["dc.contributor.author","Schmid, Adrian W."],["dc.contributor.author","Moniatte, Marc"],["dc.contributor.author","Zhang, Jing"],["dc.contributor.author","Kruse, Niels"],["dc.contributor.author","Lashuel, Hilal A."],["dc.contributor.author","Teunissen, Charlotte"],["dc.contributor.author","Schubert, Tanja"],["dc.contributor.author","Dave, Kuldip D."],["dc.contributor.author","Hutten, Samantha J."],["dc.contributor.author","Zetterberg, Henrik"],["dc.date.accessioned","2019-07-09T11:50:53Z"],["dc.date.available","2019-07-09T11:50:53Z"],["dc.date.issued","2019"],["dc.description.abstract","α-Synuclein is the major component of Lewy bodies and a candidate biomarker for neurodegenerative diseases in which Lewy bodies are common, including Parkinson's disease and dementia with Lewy bodies. A large body of literature suggests that these disorders are characterized by reduced concentrations of α-synuclein in cerebrospinal fluid (CSF), with overlapping concentrations compared to healthy controls and variability across studies. Several reasons can account for this variability, including technical ones, such as inter-assay and inter-laboratory variation (reproducibility). We compared four immunochemical methods for the quantification of α-synuclein concentration in 50 unique CSF samples. All methods were designed to capture most of the existing α-synuclein forms in CSF ('total' α-synuclein). Each of the four methods showed high analytical precision, excellent correlation between laboratories (R2 0.83-0.99), and good correlation with each other (R2 0.64-0.93), although the slopes of the regression lines were different between the four immunoassays. The use of common reference CSF samples decreased the differences in α-synuclein concentration between detection methods and technologies. Pilot data on an immunoprecipitation mass spectrometry (IP-MS) method is also presented. Our results suggest that the four immunochemical methods and the IP-MS method measure similar forms of α-synuclein and that a common reference material would allow harmonization of results between immunoassays."],["dc.identifier.doi","10.1111/jnc.14569"],["dc.identifier.pmid","30125936"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16020"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59849"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Antibody‐based methods for the measurement of α‐synuclein concentration in human cerebrospinal fluid – method comparison and round robin study"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2517"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","2530"],["dc.bibliographiccitation.volume","132"],["dc.contributor.author","Cotte, S."],["dc.contributor.author","von Ahsen, Nicolas"],["dc.contributor.author","Kruse, Niels"],["dc.contributor.author","Huber, B."],["dc.contributor.author","Winkelmann, Alexander"],["dc.contributor.author","Zettl, Uwe K."],["dc.contributor.author","Starck, Michaela"],["dc.contributor.author","Koenig, N."],["dc.contributor.author","Tellez, N."],["dc.contributor.author","Doerr, J."],["dc.contributor.author","Paul, Friedemann"],["dc.contributor.author","Zipp, Frauke"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Koepsell, Hermann"],["dc.contributor.author","Pannek, H."],["dc.contributor.author","Montalban, Xavier"],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Chan, A."],["dc.date.accessioned","2018-11-07T11:24:34Z"],["dc.date.available","2018-11-07T11:24:34Z"],["dc.date.issued","2009"],["dc.description.abstract","Escalation therapy with mitoxantrone (MX) in highly active multiple sclerosis is limited by partially dose-dependent side-effects. Predictors of therapeutic response may result in individualized risk stratification and MX dosing. ATP-binding cassette-transporters ABCB1 and ABCG2 represent multi-drug resistance mechanisms involved in active cellular MX efflux. Here, we investigated the role of ABC-gene single nucleotide polymorphisms (SNPs) for clinical MX response, corroborated by experimental in vitro and in vivo data. Frequencies of ABCB1 2677GT, 3435CT and five ABCG2-SNPs were analysed in 832 multiple sclerosis patients (Germany, Spain) and 264 healthy donors. Using a flow-cytometry-based in vitro assay, MX efflux in leukocytes from individuals with variant alleles in both ABC-genes (designated genotype ABCB1/ABCG2-L(ow), 22.2 of patients) was 37.7 lower than from individuals homozygous for common alleles (ABCB1/ABCG2-H(igh), P 0.05, 14.8 of patients), resulting in genotype-dependent MX accumulation and cell death. Addition of glucocorticosteroids (GCs) inhibited MX efflux in vitro. ABC-transporters were highly expressed in leukocyte subsets, glial and neuronal cells as well as myocardium, i.e. cells/tissues potentially affected by MX therapy. In vivo significance was further corroborated in experimental autoimmune encephalomyelitis in Abcg2(/) animals. Using a MX dose titrated to be ineffective in wild-type animals, disease course and histopathology in Abcg2(/) mice were strongly ameliorated. Retrospective clinical analysis in MX monotherapy patients (n 155) used expanded disability status scale, relapse rate and multiple sclerosis functional composite as major outcome parameters. The clinical response rate [overall 121 of 155 patients (78.1)] increased significantly with genotypes associated with decreasing ABCB1/ABCG2-function [ABCB1/ABCG2-H 15/24 (62.5) responders, ABCB1/ABCG2-I(ntermediate) 78/98 (79.6), ABCB1/ABCG2-L 28/33 (84.8), exact Cochran-Armitage test P 0.039]. The odds ratio for response was 1.9 (95 CI 1.03.5) with each increase in ABCB1/ABCG2 score (from ABCB1/ABCG2-H to I-, and I to L). In 36 patients with severe cardiac or haematological side effects no statistically relevant difference in genotype frequency was observed. However, one patient with biopsy proven cardiomyopathy only after 24 mg/m(2) MX exhibited a rare genotype with variant, partly homozygous alleles in 3 ABC-transporter genes. In conclusion, SNPs in ABC-transporter genes may serve as pharmacogenetic markers associated with clinical response to MX therapy in multiple sclerosis. Combined MX/GC-treatment warrants further investigation."],["dc.description.sponsorship","Merck Serono, Germany"],["dc.identifier.doi","10.1093/brain/awp164"],["dc.identifier.isi","000269963600021"],["dc.identifier.pmid","19605531"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6073"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56436"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0006-8950"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","ABC-transporter gene-polymorphisms are potential pharmacogenetic markers for mitoxantrone response in multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["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.firstpage","2248"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","2263"],["dc.bibliographiccitation.volume","133"],["dc.contributor.author","Linker, Ralf A."],["dc.contributor.author","Lee, De-Hyung"],["dc.contributor.author","Demir, Seray"],["dc.contributor.author","Wiese, Stefan"],["dc.contributor.author","Kruse, Niels"],["dc.contributor.author","Siglienti, Ines"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Neumann, Harald"],["dc.contributor.author","Sendtner, Michael"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Gold, Ralf"],["dc.date.accessioned","2018-11-07T08:40:38Z"],["dc.date.available","2018-11-07T08:40:38Z"],["dc.date.issued","2010"],["dc.description.abstract","Brain-derived neurotrophic factor plays a key role in neuronal and axonal survival. Brain-derived neurotrophic factor is expressed in the immune cells in lesions of experimental autoimmune encephalomyelitis and multiple sclerosis, thus potentially mediating neuroprotective effects. We investigated the functional role of brain-derived neurotrophic factor in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Mice deficient for brain-derived neurotrophic factor in immune cells displayed an attenuated immune response in the acute phase of experimental autoimmune encephalomyelitis, but progressive disability with enhanced axonal loss in the chronic phase of the disease. In mice deficient for central nervous system-derived brain-derived neurotrophic factor via glial fibrillary acidic protein-crescentin-mediated deletion, a more severe course of experimental autoimmune encephalomyelitis and an overall increased axonal loss was observed. In a lentiviral approach, injection of brain-derived neurotrophic factor-overexpressing T cells led to a less severe course of experimental autoimmune encephalomyelitis and direct axonal protection. Our data imply a functional role of brain-derived neurotrophic factor in autoimmune demyelination by mediating axon protection."],["dc.identifier.doi","10.1093/brain/awq179"],["dc.identifier.isi","000280982700010"],["dc.identifier.pmid","20826430"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6203"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19277"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0006-8950"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Functional role of brain-derived neurotrophic factor in neuroprotective autoimmunity: therapeutic implications in a model of multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","mds.28738"],["dc.bibliographiccitation.firstpage","2874"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Movement Disorders"],["dc.bibliographiccitation.lastpage","2887"],["dc.bibliographiccitation.volume","36"],["dc.contributor.affiliation","Schulz, Isabel; 1\r\nParacelsus‐Elena‐Klinik\r\nKassel Germany"],["dc.contributor.affiliation","Kruse, Niels; 2\r\nDepartment of Neuropathology\r\nUniversity Medical Centre Goettingen\r\nGoettingen Germany"],["dc.contributor.affiliation","Gera, Roland G.; 3\r\nDepartment of Medical Statistics\r\nUniversity Medical Centre Goettingen\r\nGoettingen Germany"],["dc.contributor.affiliation","Kremer, Thomas; 4\r\nRoche Pharmaceutical Research and Early Development\r\nNRD Neuroscience and Rare Disease, Roche Innovation Center Basel, F. Hoffmann‐La Roche Ltd\r\nBasel Switzerland"],["dc.contributor.affiliation","Cedarbaum, Jesse; 5\r\nCoeruleus Clinical Sciences LLC\r\nWoodbidge Connecticut USA"],["dc.contributor.affiliation","Barbour, Robin; 7\r\nProthena Biosciences Inc.\r\nSan Francisco California USA"],["dc.contributor.affiliation","Zago, Wagner; 7\r\nProthena Biosciences Inc.\r\nSan Francisco California USA"],["dc.contributor.affiliation","Schade, Sebastian; 8\r\nDepartment of Neurology\r\nUniversity Medical Centre Goettingen\r\nGoettingen Germany"],["dc.contributor.affiliation","Otte, Birgit; 8\r\nDepartment of Neurology\r\nUniversity Medical Centre Goettingen\r\nGoettingen Germany"],["dc.contributor.affiliation","Bartl, Michael; 8\r\nDepartment of Neurology\r\nUniversity Medical Centre Goettingen\r\nGoettingen Germany"],["dc.contributor.affiliation","Hutten, Samantha J.; 9\r\nThe Michael J. Fox Foundation for Parkinson's Research\r\nNew York New York USA"],["dc.contributor.affiliation","Trenkwalder, Claudia; 1\r\nParacelsus‐Elena‐Klinik\r\nKassel Germany"],["dc.contributor.author","Schulz, Isabel"],["dc.contributor.author","Kruse, Niels"],["dc.contributor.author","Gera, Roland G."],["dc.contributor.author","Kremer, Thomas"],["dc.contributor.author","Cedarbaum, Jesse"],["dc.contributor.author","Barbour, Robin"],["dc.contributor.author","Zago, Wagner"],["dc.contributor.author","Schade, Sebastian"],["dc.contributor.author","Otte, Birgit"],["dc.contributor.author","Bartl, Michael"],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Hutten, Samantha J."],["dc.contributor.author","Trenkwalder, Claudia"],["dc.date.accessioned","2021-09-01T06:42:14Z"],["dc.date.available","2021-09-01T06:42:14Z"],["dc.date.issued","2021"],["dc.date.updated","2022-03-21T11:31:27Z"],["dc.description.abstract","ABSTRACT Background Objective diagnostic biomarkers are needed to support a clinical diagnosis. Objectives To analyze markers in various neurodegenerative disorders to identify diagnostic biomarker candidates for mainly α‐synuclein (aSyn)‐related disorders (ASRD) in serum and/or cerebrospinal fluid (CSF). Methods Upon initial testing of commercially available kits or published protocols for the quantification of the candidate markers, assays for the following were selected: total and phosphorylated aSyn (pS129aSyn), neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), tau protein (tau), ubiquitin C‐terminal hydrolase L1 (UCHL‐1), glial fibrillary acidic protein (GFAP), calcium‐binding protein B (S100B), soluble triggering receptor expressed on myeloid cells 2 (sTREM‐2), and chitinase‐3‐like protein 1 (YKL‐40). The cohort comprised participants with Parkinson's disease (PD, n = 151), multiple system atrophy (MSA, n = 17), dementia with Lewy bodies (DLB, n = 45), tau protein‐related neurodegenerative disorders (n = 80, comprising patients with progressive supranuclear palsy (PSP, n = 38), corticobasal syndrome (CBS, n = 16), Alzheimer's disease (AD, n = 11), and frontotemporal degeneration/amyotrophic lateral sclerosis (FTD/ALS, n = 15), as well as healthy controls (HC, n = 20). Receiver operating curves (ROC) with area under the curves (AUC) are given for each marker. Results CSF total aSyn was decreased. NfL, pNfH, UCHL‐1, GFAP, S100B, and sTREM‐2 were increased in patients with neurodegenerative disease versus HC (P < 0.05). As expected, some of the markers were highest in AD (i.e., UCHL‐1, GFAP, S100B, sTREM‐2, YKL‐40). Within ASRD, CSF NfL levels were higher in MSA than PD and DLB (P < 0.05). Comparing PD to HC, interesting serum markers were S100B (AUC: 0.86), sTREM2 (AUC: 0.87), and NfL (AUC: 0.78). CSF S100B and serum GFAP were highest in DLB. Conclusions Levels of most marker candidates tested in serum and CSF significantly differed between disease groups and HC. In the stratification of PD versus other tau‐ or aSyn‐related conditions, CSF NfL levels best discriminated PD and MSA. CSF S100B and serum GFAP best discriminated PD and DLB. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society."],["dc.identifier.doi","10.1002/mds.28738"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/89011"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-455"],["dc.relation.eissn","1531-8257"],["dc.relation.issn","0885-3185"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited."],["dc.title","Systematic Assessment of 10 Biomarker Candidates Focusing on α‐Synuclein‐Related Disorders"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1259"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Diagnostics"],["dc.bibliographiccitation.volume","12"],["dc.contributor.affiliation","Emdina, Anna; 1Department of Neurology, University Medical Center Göttingen, 37075 Göttingen, Germany; anna.emdina@stud.uni-goettingen.de (A.E.); d.varges@med.uni-goettingen.de (D.V.); sabine.nuhn@med.uni-goettingen.de (S.N.); stefan.goebel@med.uni-goettingen.de (S.G.); timothy.bunck@med.uni-goettingen.de (T.B.); fabian.maass@med.uni-goettingen.de (F.M.); matthias.schmitz@med.uni-goettingen.de (M.S.); franc.llorens@gmail.com (F.L.); brit.mollenhauer@med.uni-goettingen.de (B.M.); ingazerr@med.uni-goettingen.de (I.Z.)"],["dc.contributor.affiliation","Hermann, Peter; 1Department of Neurology, University Medical Center Göttingen, 37075 Göttingen, Germany; anna.emdina@stud.uni-goettingen.de (A.E.); d.varges@med.uni-goettingen.de (D.V.); sabine.nuhn@med.uni-goettingen.de (S.N.); stefan.goebel@med.uni-goettingen.de (S.G.); timothy.bunck@med.uni-goettingen.de (T.B.); fabian.maass@med.uni-goettingen.de (F.M.); matthias.schmitz@med.uni-goettingen.de (M.S.); franc.llorens@gmail.com (F.L.); brit.mollenhauer@med.uni-goettingen.de (B.M.); ingazerr@med.uni-goettingen.de (I.Z.)"],["dc.contributor.affiliation","Varges, Daniela; 1Department of Neurology, University Medical Center Göttingen, 37075 Göttingen, Germany; anna.emdina@stud.uni-goettingen.de (A.E.); d.varges@med.uni-goettingen.de (D.V.); sabine.nuhn@med.uni-goettingen.de (S.N.); stefan.goebel@med.uni-goettingen.de (S.G.); timothy.bunck@med.uni-goettingen.de (T.B.); fabian.maass@med.uni-goettingen.de (F.M.); matthias.schmitz@med.uni-goettingen.de (M.S.); franc.llorens@gmail.com (F.L.); brit.mollenhauer@med.uni-goettingen.de (B.M.); ingazerr@med.uni-goettingen.de (I.Z.)"],["dc.contributor.affiliation","Nuhn, Sabine; 1Department of Neurology, University Medical Center Göttingen, 37075 Göttingen, Germany; anna.emdina@stud.uni-goettingen.de (A.E.); d.varges@med.uni-goettingen.de (D.V.); sabine.nuhn@med.uni-goettingen.de (S.N.); stefan.goebel@med.uni-goettingen.de (S.G.); timothy.bunck@med.uni-goettingen.de (T.B.); fabian.maass@med.uni-goettingen.de (F.M.); matthias.schmitz@med.uni-goettingen.de (M.S.); franc.llorens@gmail.com (F.L.); brit.mollenhauer@med.uni-goettingen.de (B.M.); ingazerr@med.uni-goettingen.de (I.Z.)"],["dc.contributor.affiliation","Goebel, Stefan; 1Department of Neurology, University Medical Center Göttingen, 37075 Göttingen, Germany; anna.emdina@stud.uni-goettingen.de (A.E.); d.varges@med.uni-goettingen.de (D.V.); sabine.nuhn@med.uni-goettingen.de (S.N.); stefan.goebel@med.uni-goettingen.de (S.G.); timothy.bunck@med.uni-goettingen.de (T.B.); fabian.maass@med.uni-goettingen.de (F.M.); matthias.schmitz@med.uni-goettingen.de (M.S.); franc.llorens@gmail.com (F.L.); brit.mollenhauer@med.uni-goettingen.de (B.M.); ingazerr@med.uni-goettingen.de (I.Z.)"],["dc.contributor.affiliation","Bunck, Timothy; 1Department of Neurology, University Medical Center Göttingen, 37075 Göttingen, Germany; anna.emdina@stud.uni-goettingen.de (A.E.); d.varges@med.uni-goettingen.de (D.V.); sabine.nuhn@med.uni-goettingen.de (S.N.); stefan.goebel@med.uni-goettingen.de (S.G.); timothy.bunck@med.uni-goettingen.de (T.B.); fabian.maass@med.uni-goettingen.de (F.M.); matthias.schmitz@med.uni-goettingen.de (M.S.); franc.llorens@gmail.com (F.L.); brit.mollenhauer@med.uni-goettingen.de (B.M.); ingazerr@med.uni-goettingen.de (I.Z.)"],["dc.contributor.affiliation","Maass, Fabian; 1Department of Neurology, University Medical Center Göttingen, 37075 Göttingen, Germany; anna.emdina@stud.uni-goettingen.de (A.E.); d.varges@med.uni-goettingen.de (D.V.); sabine.nuhn@med.uni-goettingen.de (S.N.); stefan.goebel@med.uni-goettingen.de (S.G.); timothy.bunck@med.uni-goettingen.de (T.B.); fabian.maass@med.uni-goettingen.de (F.M.); matthias.schmitz@med.uni-goettingen.de (M.S.); franc.llorens@gmail.com (F.L.); brit.mollenhauer@med.uni-goettingen.de (B.M.); ingazerr@med.uni-goettingen.de (I.Z.)"],["dc.contributor.affiliation","Schmitz, Matthias; 1Department of Neurology, University Medical Center Göttingen, 37075 Göttingen, Germany; anna.emdina@stud.uni-goettingen.de (A.E.); d.varges@med.uni-goettingen.de (D.V.); sabine.nuhn@med.uni-goettingen.de (S.N.); stefan.goebel@med.uni-goettingen.de (S.G.); timothy.bunck@med.uni-goettingen.de (T.B.); fabian.maass@med.uni-goettingen.de (F.M.); matthias.schmitz@med.uni-goettingen.de (M.S.); franc.llorens@gmail.com (F.L.); brit.mollenhauer@med.uni-goettingen.de (B.M.); ingazerr@med.uni-goettingen.de (I.Z.)"],["dc.contributor.affiliation","Llorens, Franc; 1Department of Neurology, University Medical Center Göttingen, 37075 Göttingen, Germany; anna.emdina@stud.uni-goettingen.de (A.E.); d.varges@med.uni-goettingen.de (D.V.); sabine.nuhn@med.uni-goettingen.de (S.N.); stefan.goebel@med.uni-goettingen.de (S.G.); timothy.bunck@med.uni-goettingen.de (T.B.); fabian.maass@med.uni-goettingen.de (F.M.); matthias.schmitz@med.uni-goettingen.de (M.S.); franc.llorens@gmail.com (F.L.); brit.mollenhauer@med.uni-goettingen.de (B.M.); ingazerr@med.uni-goettingen.de (I.Z.)"],["dc.contributor.affiliation","Kruse, Niels; 4Department of Neuropathology, University Medical Centre Göttingen, 37075 Göttingen, Germany; n.kruse@med.uni-goettingen.de"],["dc.contributor.affiliation","Lingor, Paul; 5Department of Neurology, Klinikum Rechts der Isar, Technical University of Munich, 80333 Munich, Germany; paul.lingor@tum.de"],["dc.contributor.affiliation","Mollenhauer, Brit; 1Department of Neurology, University Medical Center Göttingen, 37075 Göttingen, Germany; anna.emdina@stud.uni-goettingen.de (A.E.); d.varges@med.uni-goettingen.de (D.V.); sabine.nuhn@med.uni-goettingen.de (S.N.); stefan.goebel@med.uni-goettingen.de (S.G.); timothy.bunck@med.uni-goettingen.de (T.B.); fabian.maass@med.uni-goettingen.de (F.M.); matthias.schmitz@med.uni-goettingen.de (M.S.); franc.llorens@gmail.com (F.L.); brit.mollenhauer@med.uni-goettingen.de (B.M.); ingazerr@med.uni-goettingen.de (I.Z.)"],["dc.contributor.affiliation","Zerr, Inga; 1Department of Neurology, University Medical Center Göttingen, 37075 Göttingen, Germany; anna.emdina@stud.uni-goettingen.de (A.E.); d.varges@med.uni-goettingen.de (D.V.); sabine.nuhn@med.uni-goettingen.de (S.N.); stefan.goebel@med.uni-goettingen.de (S.G.); timothy.bunck@med.uni-goettingen.de (T.B.); fabian.maass@med.uni-goettingen.de (F.M.); matthias.schmitz@med.uni-goettingen.de (M.S.); franc.llorens@gmail.com (F.L.); brit.mollenhauer@med.uni-goettingen.de (B.M.); ingazerr@med.uni-goettingen.de (I.Z.)"],["dc.contributor.author","Emdina, Anna"],["dc.contributor.author","Hermann, Peter"],["dc.contributor.author","Varges, Daniela"],["dc.contributor.author","Nuhn, Sabine"],["dc.contributor.author","Goebel, Stefan"],["dc.contributor.author","Bunck, Timothy"],["dc.contributor.author","Maass, Fabian"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Llorens, Franc"],["dc.contributor.author","Kruse, Niels"],["dc.contributor.author","Zerr, Inga"],["dc.contributor.author","Lingor, Paul"],["dc.contributor.author","Mollenhauer, Brit"],["dc.date.accessioned","2022-06-01T09:39:57Z"],["dc.date.available","2022-06-01T09:39:57Z"],["dc.date.issued","2022"],["dc.date.updated","2022-06-05T20:43:26Z"],["dc.description.abstract","Biomarkers are increasingly recognized as tools in the diagnosis and prognosis of neurodegenerative diseases. No fluid biomarker for Parkinson’s disease (PD) has been established to date, but α-synuclein, a major component of Lewy bodies in PD and dementia with Lewy bodies (DLB), has become a promising candidate. Here, we investigated CSF α-synuclein in patients with PD (n = 28), PDD (n = 8), and DLB (n = 5), applying an electrochemiluminescence immunoassay. Median values were non-significantly (p = 0.430) higher in patients with PDD and DLB (287 pg/mL) than in PD (236 pg/mL). A group of n = 36 primarily non-demented patients with PD and PDD was clinically followed for up to two years. A higher baseline α-synuclein was associated with increases in Hoehn and Yahr classifications (p = 0.019) and Beck Depression Inventory scores (p < 0.001) as well as worse performance in Trail Making Test A (p = 0.017), Trail Making Test B (p = 0.043), and the Boston Naming Test (p = 0.002) at follow-up. Surprisingly, higher levels were associated with a better performance in semantic verbal fluency tests (p = 0.046). In summary, CSF α-synuclein may be a potential prognostic marker for disease progression, affective symptoms, and executive cognitive function in PD. Larger-scaled studies have to validate these findings and the discordant results for single cognitive tests in this exploratory investigation."],["dc.identifier.doi","10.3390/diagnostics12051259"],["dc.identifier.pii","diagnostics12051259"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/108601"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-572"],["dc.relation.eissn","2075-4418"],["dc.title","Baseline Cerebrospinal Fluid α-Synuclein in Parkinson’s Disease Is Associated with Disease Progression and Cognitive Decline"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e1004741"],["dc.bibliographiccitation.journal","PLoS Genetics"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Lazaro, Diana F."],["dc.contributor.author","Rodrigues, Eva F."],["dc.contributor.author","Langohr, Ramona"],["dc.contributor.author","Shahpasandzadeh, Hedieh"],["dc.contributor.author","Ribeiro, Thales"],["dc.contributor.author","Guerreiro, Patricia"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Kroehnert, Katharina"],["dc.contributor.author","Klucken, Jochen"],["dc.contributor.author","Pereira, Marcos D."],["dc.contributor.author","Popova, Blagovesta"],["dc.contributor.author","Kruse, Niels"],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Rizzoli, Silvio"],["dc.contributor.author","Braus, Gerhard H."],["dc.contributor.author","Danzer, Karin M."],["dc.contributor.author","Outeiro, Tiago F."],["dc.date.accessioned","2017-09-07T11:45:25Z"],["dc.date.available","2017-09-07T11:45:25Z"],["dc.date.issued","2014"],["dc.description.abstract","Aggregation of alpha-synuclein (ASYN) in Lewy bodies and Lewy neurites is the typical pathological hallmark of Parkinson's disease (PD) and other synucleinopathies. Furthermore, mutations in the gene encoding for ASYN are associated with familial and sporadic forms of PD, suggesting this protein plays a central role in the disease. However, the precise contribution of ASYN to neuronal dysfunction and death is unclear. There is intense debate about the nature of the toxic species of ASYN and little is known about the molecular determinants of oligomerization and aggregation of ASYN in the cell. In order to clarify the effects of different mutations on the propensity of ASYN to oligomerize and aggregate, we assembled a panel of 19 ASYN variants and compared their behaviour. We found that familial mutants linked to PD (A30P, E46K, H50Q, G51D and A53T) exhibited identical propensities to oligomerize in living cells, but had distinct abilities to form inclusions. While the A30P mutant reduced the percentage of cells with inclusions, the E46K mutant had the opposite effect. Interestingly, artificial proline mutants designed to interfere with the helical structure of the N-terminal domain, showed increased propensity to form oligomeric species rather than inclusions. Moreover, lysine substitution mutants increased oligomerization and altered the pattern of aggregation. Altogether, our data shed light into the molecular effects of ASYN mutations in a cellular context, and established a common ground for the study of genetic and pharmacological modulators of the aggregation process, opening new perspectives for therapeutic intervention in PD and other synucleinopathies."],["dc.identifier.doi","10.1371/journal.pgen.1004741"],["dc.identifier.gro","3142024"],["dc.identifier.isi","000345455200011"],["dc.identifier.pmid","25393002"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11136"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/3701"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1553-7404"],["dc.relation.issn","1553-7390"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Systematic Comparison of the Effects of Alpha-synuclein Mutations on Its Oligomerization and Aggregation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","293"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","MULTIPLE SCLEROSIS"],["dc.bibliographiccitation.lastpage","302"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Blecharz, Kinga G."],["dc.contributor.author","Haghikia, Aiden"],["dc.contributor.author","Stasiolek, Mariusz"],["dc.contributor.author","Kruse, Niels"],["dc.contributor.author","Drenckhahn, Detlev"],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Roewer, Norbert"],["dc.contributor.author","Chan, Andrew"],["dc.contributor.author","Foerster, Carola Y."],["dc.date.accessioned","2018-11-07T08:45:36Z"],["dc.date.available","2018-11-07T08:45:36Z"],["dc.date.issued","2010"],["dc.description.abstract","Compromised blood-brain barrier integrity is a major hallmark of active multiple sclerosis (MS). Alterations in brain endothelial tight junction protein and gene expression occur early during neuroinflammation but there is little known about the underlying mechanisms. In this study, we analysed barrier compromising effects of sera from MS patients and barrier restoring effects of glucocorticoids on blood-brain barrier integrity in vitro. cEND murine brain microvascular endothelial cell monolayers were incubated with sera from patients in active phase of disease or in relapse. Data were compared with effects of the glucocorticoid dexamethasone alone or in combination with MS sera on barrier integrity. Tight junction protein levels and gene expression were evaluated concomitant with barrier integrity. We reveal down-regulation of claudin-5 and occludin protein and mRNA and an accompanying upregulation in expression of matrix metalloproteinase MMP-9 after incubation with serum from active disease and remission and also a minor reconstitution of barrier functions related to dexamethasone treatment. Moreover, we for the first time describe downregulation of claudin-5 and occludin protein after incubation of cEND cells with sera from patients in remission phase of MS. Our findings reveal direct and differential effects of MS sera on blood-brain barrier integrity."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [SFB688-TPA5, SFB-TPA1 RG]"],["dc.identifier.doi","10.1177/1352458509358189"],["dc.identifier.isi","000275179200004"],["dc.identifier.pmid","20203147"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13047"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20482"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Sage Publications Ltd"],["dc.relation.issn","1352-4585"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Glucocorticoid effects on endothelial barrier function in the murine brain endothelial cell line cEND incubated with sera from patients with multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","24"],["dc.bibliographiccitation.journal","BMC Neurology"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Fischer, Charlotte"],["dc.contributor.author","Kleinschnitz, Konstanze"],["dc.contributor.author","Wrede, Arne"],["dc.contributor.author","Muth, Ingrid E."],["dc.contributor.author","Kruse, Niels"],["dc.contributor.author","Nishino, Ichizo"],["dc.contributor.author","Schmidt, Jens"],["dc.date.accessioned","2018-11-07T09:27:04Z"],["dc.date.available","2018-11-07T09:27:04Z"],["dc.date.issued","2013"],["dc.description.abstract","Background: Mutations of the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine-kinase (GNE)-gene are causally related to GNE myopathy. Yet, underlying pathomechanisms of muscle fibre damage have remained elusive. In sporadic inclusion body myositis (sIBM), the pro-inflammatory cell-stress mediators alpha B-crystallin and inducible nitric oxide synthase (iNOS) are crucial markers of the disease pathology. Methods: 10 muscle biopsies from GNE myopathy patients were analyzed for mRNA-expression of markers of cell-stress, inflammation and beta-amyloid and compared to non-myopathic controls. Using double-labeling immunohistochemistry, serial sections of skeletal muscle biopsies were stained for amyloid precursor protein (APP), major histocompatibility complex (MHC)-I, alpha B-crystallin, neural cell adhesion molecule (NCAM), interleukin (IL)-1 beta, beta-amyloid, iNOS, and phosphorylated neurofilament (P-neurofilament) as well as hematoxylin/eosin histochemistry. Corresponding areas of all biopsies with a total of 2,817 muscle fibres were quantitatively assessed for all markers. Results: mRNA-expression of APP, NCAM, iNOS, TNF-alpha and TGF-beta was higher in GNE myopathy compared to controls, yet this was not statistically significant. The mRNA-expression of APP and alpha B-crystallin significantly correlated with the expression of several pro-inflammatory and cell-stress-associated markers as NCAM, IL-1 beta, TGF-beta, CCL-3, and CCL4. By immunohistochemistry, alpha B-crystallin and iNOS were co-upregulated and the number of fibres positive for alpha B-crystallin, NCAM, MHC-I and iNOS significantly correlated with each other. A large fraction of fibres positive for alpha B-crystallin were double positive for iNOS and vice-versa. Moreover, several fibres with structural abnormalities were positive for alpha B-crystallin and iNOS. Notably, particularly normal appearing fibres displayed an overexpression of these molecules. Conclusions: The cell-stress molecules alpha B-crystallin and iNOS are overexpressed in GNE myopathy muscle and may identify early disease mechanisms. The data help to better understand the pathology of GNE myopathy."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2013"],["dc.identifier.doi","10.1186/1471-2377-13-24"],["dc.identifier.isi","000317485500001"],["dc.identifier.pmid","23496965"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8778"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30452"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1471-2377"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Cell stress molecules in the skeletal muscle of GNE myopathy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","UNSP 179"],["dc.bibliographiccitation.journal","Frontiers in Neurology"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Andreasson, Ulf"],["dc.contributor.author","Perret-Liaudet, Armand"],["dc.contributor.author","van Waalwijk van Doorn, Linda J. C."],["dc.contributor.author","Blennow, Kaj"],["dc.contributor.author","Chiasserini, Davide"],["dc.contributor.author","Engelborghs, Sebastiaan"],["dc.contributor.author","Fladby, Tormod"],["dc.contributor.author","Genc, Sermin"],["dc.contributor.author","Kruse, Niels"],["dc.contributor.author","Kuipenj, H. Bea"],["dc.contributor.author","Kulic, Luka"],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Mroczko, Barbara"],["dc.contributor.author","Pametti, Lucille"],["dc.contributor.author","Vanmechelen, Eugeen"],["dc.contributor.author","Verbeek, Marcel M."],["dc.contributor.author","Winblad, Bengt"],["dc.contributor.author","Zetterberg, Henrik"],["dc.contributor.author","Koel-Simmelink, Marleen J. A."],["dc.contributor.author","Teunissen, Charlotte E."],["dc.date.accessioned","2018-11-07T09:53:12Z"],["dc.date.available","2018-11-07T09:53:12Z"],["dc.date.issued","2015"],["dc.description.abstract","Biochemical markers have a central position in the diagnosis and management of patients in clinical medicine, and also in clinical research and drug development, also for brain disorders, such as Alzheimer's disease. The enzyme-linked immunosorbent assay (ELISA) is frequently used for measurement of low-abundance biomarkers. However, the quality of ELISA methods varies, which may introduce both systematic and random errors. This urges the need for more rigorous control of assay performance, regardless of its use in a research setting, in clinical routine, or drug development. The aim of a method validation is to present objective evidence that a method fulfills the requirements for its intended use. Although much has been published on which parameters to investigate in a method validation, less is available on a detailed level on how to perform the corresponding experiments. To remedy this, standard operating procedures (SOPs) with step-by-step instructions for a number of different validation parameters is included in the present work together with a validation report template, which allow for a well-ordered presentation of the results. Even though the SOPs were developed with the intended use for immunochemical methods and to be used for multicenter evaluations, most of them are generic and can be used for other technologies as well."],["dc.identifier.doi","10.3389/fneur.2015.00179"],["dc.identifier.isi","000363861800001"],["dc.identifier.pmid","26347708"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12620"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36285"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","1664-2295"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","A practical guide to immunoassay method validation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]