Kornhuber, Johannes

[["dc.bibliographiccitation.firstpage","366"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Experimental Neurology"],["dc.bibliographiccitation.lastpage","370"],["dc.bibliographiccitation.volume","223"],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Vanmechelen, Eugeen"],["dc.contributor.author","Peters, Oliver"],["dc.contributor.author","Heuser, Isabella"],["dc.contributor.author","Maier, Wolfgang"],["dc.contributor.author","Jessen, Frank"],["dc.contributor.author","Buerger, Katharina"],["dc.contributor.author","Hampel, Harald"],["dc.contributor.author","Froelich, Lutz"],["dc.contributor.author","Henn, Fritz A."],["dc.contributor.author","Falkai, Peter Gaston"],["dc.contributor.author","Ruether, Eckhart"],["dc.contributor.author","Jahn, Holger"],["dc.contributor.author","Luckhaus, C. H."],["dc.contributor.author","Perneczky, Robert"],["dc.contributor.author","Schmidtke, K."],["dc.contributor.author","Schroeder, J."],["dc.contributor.author","Kessler, H."],["dc.contributor.author","Pantel, Johannes"],["dc.contributor.author","Gertz, H.-J."],["dc.contributor.author","Vanderstichele, Hugo"],["dc.contributor.author","de Meyer, G."],["dc.contributor.author","Shapiro, F."],["dc.contributor.author","Wolf, S."],["dc.contributor.author","Bibl, Mirko"],["dc.contributor.author","Wiltfang, J."],["dc.date.accessioned","2018-11-07T08:42:36Z"],["dc.date.available","2018-11-07T08:42:36Z"],["dc.date.issued","2010"],["dc.description.abstract","We measured concentrations of to peptides 1-42 and 1-40, and their ratio in plasma of patients carefully categorized clinically and neurochemically as having AD or other dementias with a newly commercially available multiplexing assay, characterized by reasonable laboratory performance (intra-assay imprecision in the range of 1.3-3.8% for A beta 1-42, and 1.8-4.1% for A beta 1-40, inter-assay imprecision for A beta 1-42, A beta 1-40, and A beta 1-42/A beta 1-40 concentration ratio in the range of 2.3-11.5%, 2.2-10.4% and 42-9.7%, respectively). Patients with AD or mild cognitive impairment of AD type (MCI-AD) whose clinical diagnosis was supported with CSF biomarkers (n = 193) had significantly lower A beta 1-42 plasma concentrations (p<0.007), and A beta 1-42/1-40 ratios (p<0.003) compared to patients with other dementias and MCI of other types (n = 64). No significant differences between persons with MCI of AD type and patients with early AD were observed, or between MCI of other types versus patients with early dementia of other types. Our findings reconfirm the hypothesis that alterations of biomarker concentrations occur early in a preclinical AD stage and that these alterations are also reflected in plasma. (C) 2009 Published by Elsevier Inc."],["dc.identifier.doi","10.1016/j.expneurol.2009.07.024"],["dc.identifier.isi","000277743700015"],["dc.identifier.pmid","19664622"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19739"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Inc Elsevier Science"],["dc.relation.issn","0014-4886"],["dc.title","Amyloid beta peptides in plasma in early diagnosis of Alzheimer's disease: A multicenter study with multiplexing"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","379"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Neurology"],["dc.bibliographiccitation.lastpage","386"],["dc.bibliographiccitation.volume","78"],["dc.contributor.author","Wagner, M."],["dc.contributor.author","Wolf, S."],["dc.contributor.author","Reischies, Friedel M."],["dc.contributor.author","Daerr, M."],["dc.contributor.author","Wolfsgruber, S."],["dc.contributor.author","Jessen, Frank"],["dc.contributor.author","Popp, J."],["dc.contributor.author","Maier, Wolfgang"],["dc.contributor.author","Huell, Michael"],["dc.contributor.author","Froelich, Lutz"],["dc.contributor.author","Hampel, Harald"],["dc.contributor.author","Perneczky, Robert"],["dc.contributor.author","Peters, Oliver"],["dc.contributor.author","Jahn, Holger"],["dc.contributor.author","Luckhaus, C."],["dc.contributor.author","Gertz, H.-J."],["dc.contributor.author","Schroeder, J."],["dc.contributor.author","Pantel, Johannes"],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Wiltfang, J."],["dc.date.accessioned","2018-11-07T09:13:50Z"],["dc.date.available","2018-11-07T09:13:50Z"],["dc.date.issued","2012"],["dc.description.abstract","Objective: To compare cued recall measures with other memory and nonmemory tests regarding their association with a biomarker profile indicative of Alzheimer disease (AD) in CSF among patients with mild cognitive impairment (MCI). Methods: Data were obtained by the German Dementia Competence Network. A total of 185 memory clinic patients fulfilling broad criteria for MCI (1 SD deficit in memory tests or in nonmemory tests) were assessed with an extended neuropsychological battery, which included the Free and Cued Selective Reminding Test (FCSRT), the word list learning task from the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery (CERAD-NP), and the Logical Memory (LM) paragraph recall test from the Wechsler Memory Scale-Revised. CSF was obtained from all patients. Results: A total of 74 out of 185 subjects with MCI (40%) had a CSF profile consistent with AD (A beta(1-42)/tau ratio; CSF AD + group). FCSRT measures reflecting both free and cued recall discriminated best between CSF AD + and CSF AD - patients, and significantly improved CSF AD classification accuracy, as compared with CERAD delayed recall and LM delayed recall. Conclusions: Cued recall deficits are most closely associated with CSF biomarkers indicative of AD in subjects with MCI. This novel finding complements results from prospective clinical studies and provides further empirical support for cued recall as a specific indicator of prodromal AD, in line with recently proposed research criteria. Neurology (R) 2012; 78: 379-386"],["dc.identifier.doi","10.1212/WNL.0b013e318245f447"],["dc.identifier.isi","000300392000007"],["dc.identifier.pmid","22238414"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27260"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","1526-632X"],["dc.relation.issn","0028-3878"],["dc.title","Biomarker validation of a cued recall memory deficit in prodromal Alzheimer disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","872"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Alzheimer's & Dementia"],["dc.bibliographiccitation.lastpage","881"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Louwersheimer, Eva"],["dc.contributor.author","Wolfsgruber, Steffen"],["dc.contributor.author","Espinosa, Ana"],["dc.contributor.author","Lacour, André"],["dc.contributor.author","Heilmann-Heimbach, Stefanie"],["dc.contributor.author","Alegret, Montserrat"],["dc.contributor.author","Hernández, Isabel"],["dc.contributor.author","Rosende-Roca, Maitée"],["dc.contributor.author","Tárraga, Lluís"],["dc.contributor.author","Boada, Mercè"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Peters, Oliver"],["dc.contributor.author","Frölich, Lutz"],["dc.contributor.author","Hüll, Michael"],["dc.contributor.author","Rüther, Eckart"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Scherer, Martin"],["dc.contributor.author","Riedel-Heller, Steffi"],["dc.contributor.author","Jessen, Frank"],["dc.contributor.author","Nöthen, Markus M."],["dc.contributor.author","Maier, Wolfgang"],["dc.contributor.author","Koene, Ted"],["dc.contributor.author","Scheltens, Philip"],["dc.contributor.author","Holstege, Henne"],["dc.contributor.author","Wagner, Michael"],["dc.contributor.author","Ruiz, Agustín"],["dc.contributor.author","van der Flier, Wiesje M."],["dc.contributor.author","Becker, Tim"],["dc.contributor.author","Ramirez, Alfredo"],["dc.date.accessioned","2017-09-07T11:44:36Z"],["dc.date.available","2017-09-07T11:44:36Z"],["dc.date.issued","2016"],["dc.description.abstract","IntroductionWe evaluated the effect of Alzheimer's disease (AD) susceptibility loci on endophenotypes closely related with AD pathology in patients with mild cognitive impairment (MCI).MethodsWe selected 1730 MCI patients from four independent data sets. Weighted polygenic risk scores (PGS) were constructed of 18 non-apolipoprotein E (APOE) AD risk variants. In addition, we determined APOE genotype. AD endophenotypes were cognitive decline over time and cerebrospinal fluid (CSF) biomarkers (aβ, tau, ptau).ResultsPGS was modestly associated with cognitive decline over time, as measured by mini-mental state examination (MMSE) (β ± SE:−0.24 ± 0.10; P = .012), and with CSF levels of tau and ptau (tau: 1.38 ± 0.36, P = 1.21 × 10−4; ptau: 1.40 ± 0.36, P = 1.02 × 10−4).DiscussionIn MCI, we observed a joint effect of AD susceptibility loci on nonamyloid endophenotypes, suggesting a link of these genetic loci with neuronal degeneration in general rather than with Alzheimer-related amyloid deposition."],["dc.identifier.doi","10.1016/j.jalz.2016.01.006"],["dc.identifier.gro","3151698"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8517"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.notes.submitter","chake"],["dc.relation.issn","1552-5260"],["dc.title","Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e13950"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Jones, Lesley"],["dc.contributor.author","Holmans, Peter A."],["dc.contributor.author","Hamshere, Marian L."],["dc.contributor.author","Harold, Denise"],["dc.contributor.author","Moskvina, Valentina"],["dc.contributor.author","Ivanov, Dobril"],["dc.contributor.author","Pocklington, Andrew"],["dc.contributor.author","Abraham, Richard"],["dc.contributor.author","Hollingworth, Paul"],["dc.contributor.author","Sims, Rebecca"],["dc.contributor.author","Gerrish, Amy"],["dc.contributor.author","Pahwa, Jaspreet Singh"],["dc.contributor.author","Jones, Nicola"],["dc.contributor.author","Stretton, Alexandra"],["dc.contributor.author","Morgan, Angharad R."],["dc.contributor.author","Lovestone, Simon"],["dc.contributor.author","Powell, John"],["dc.contributor.author","Proitsi, Petroula"],["dc.contributor.author","Lupton, Michelle K."],["dc.contributor.author","Brayne, Carol"],["dc.contributor.author","Rubinsztein, David C."],["dc.contributor.author","Gill, Michael"],["dc.contributor.author","Lawlor, Brian"],["dc.contributor.author","Lynch, Aoibhinn"],["dc.contributor.author","Morgan, Kevin"],["dc.contributor.author","Brown, Kristelle S."],["dc.contributor.author","Passmore, Peter A."],["dc.contributor.author","Craig, David"],["dc.contributor.author","McGuinness, Bernadette"],["dc.contributor.author","Todd, Stephen"],["dc.contributor.author","Holmes, Clive"],["dc.contributor.author","Mann, David"],["dc.contributor.author","Smith, A. David"],["dc.contributor.author","Love, Seth"],["dc.contributor.author","Kehoe, Patrick G."],["dc.contributor.author","Mead, Simon"],["dc.contributor.author","Fox, Nick"],["dc.contributor.author","Rossor, Martin"],["dc.contributor.author","Collinge, John"],["dc.contributor.author","Maier, Wolfgang"],["dc.contributor.author","Jessen, Frank"],["dc.contributor.author","Schürmann, Britta"],["dc.contributor.author","van den Bussche, Hendrik"],["dc.contributor.author","Heuser, Isabella"],["dc.contributor.author","Peters, Oliver"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Dichgans, Martin"],["dc.contributor.author","Frölich, Lutz"],["dc.contributor.author","Hampel, Harald"],["dc.contributor.author","Hüll, Michael"],["dc.contributor.author","Rujescu, Dan"],["dc.contributor.author","Goate, Alison M."],["dc.contributor.author","Kauwe, John S. K."],["dc.contributor.author","Cruchaga, Carlos"],["dc.contributor.author","Nowotny, Petra"],["dc.contributor.author","Morris, John C."],["dc.contributor.author","Mayo, Kevin"],["dc.contributor.author","Livingston, Gill"],["dc.contributor.author","Bass, Nicholas J."],["dc.contributor.author","Gurling, Hugh"],["dc.contributor.author","McQuillin, Andrew"],["dc.contributor.author","Gwilliam, Rhian"],["dc.contributor.author","Deloukas, Panos"],["dc.contributor.author","Al-Chalabi, Ammar"],["dc.contributor.author","Shaw, Christopher E."],["dc.contributor.author","Singleton, Andrew B."],["dc.contributor.author","Guerreiro, Rita"],["dc.contributor.author","Mühleisen, Thomas W."],["dc.contributor.author","Nöthen, Markus M."],["dc.contributor.author","Moebus, Susanne"],["dc.contributor.author","Jöckel, Karl-Heinz"],["dc.contributor.author","Klopp, Norman"],["dc.contributor.author","Wichmann, H.-Erich"],["dc.contributor.author","Rüther, Eckhard"],["dc.contributor.author","Carrasquillo, Minerva M."],["dc.contributor.author","Pankratz, V. Shane"],["dc.contributor.author","Younkin, Steven G."],["dc.contributor.author","Hardy, John"],["dc.contributor.author","O'Donovan, Michael C."],["dc.contributor.author","Owen, Michael J."],["dc.contributor.author","Williams, Julie"],["dc.date.accessioned","2019-07-09T11:54:00Z"],["dc.date.available","2019-07-09T11:54:00Z"],["dc.date.issued","2010-11-15"],["dc.description.abstract","Background: Late Onset Alzheimer’s disease (LOAD) is the leading cause of dementia. Recent large genome-wide association studies (GWAS) identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes. Methodology: We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset. Principal Findings: We found a significant overrepresentation of association signals in pathways related to cholesterol metabolism and the immune response in both of the two largest genome-wide association studies for LOAD. Significance: Processes related to cholesterol metabolism and the innate immune response have previously been implicated by pathological and epidemiological studies of Alzheimer’s disease, but it has been unclear whether those findings reflected primary aetiological events or consequences of the disease process. Our independent evidence from two large studies now demonstrates that these processes are aetiologically relevant, and suggests that they may be suitable targets for novel and existing therapeutic approaches."],["dc.format.extent","11"],["dc.identifier.doi","10.1371/journal.pone.0013950"],["dc.identifier.pmid","21085570"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8307"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60547"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Genetic Evidence Implicates the Immune System and Cholesterol Metabolism in the Aetiology of Alzheimer's Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2485"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","2490"],["dc.bibliographiccitation.volume","73"],["dc.contributor.author","Wiltfang, J."],["dc.contributor.author","Otto, M."],["dc.contributor.author","Baxter, H. C."],["dc.contributor.author","Bodemer, M."],["dc.contributor.author","Steinacker, P."],["dc.contributor.author","Bahn, E."],["dc.contributor.author","Zerr, I."],["dc.contributor.author","Kornhuber, J."],["dc.contributor.author","Kretzschmar, H. A."],["dc.contributor.author","Poser, S."],["dc.contributor.author","Rüther, E."],["dc.contributor.author","Aitken, A."],["dc.date.accessioned","2017-09-07T11:44:33Z"],["dc.date.available","2017-09-07T11:44:33Z"],["dc.date.issued","1999"],["dc.description.abstract","Two-dimensional polyacrylamide gel electrophoresis of CSF has been used in the diagnosis of Creutzfeldt-Jakob disease (CJD). One of the two diagnostic protein spots was identified as isoform(s) of the 14-3-3 family of abundant brain proteins. This has led to the development of one-dimensional 14-3-3 sodium dodecyl sulfate polyacrylamide gel electrophoresis immunoblot, which is currently used to support the diagnosis of CJD. In the present study employing western blot analysis, we have identified the panel of 14-3-3 isoforms that appear in the CSF of 10 patients with CJD compared with 10 patients with other dementias. The results clearly show that the 14-3-3 isoforms β, γ, ε, and η are present in the CSF of patients with CJD and can be used to differentiate other dementias. 14-3-3η also gave a baseline signal in all patients with other dementias, including six patients with Alzheimer's disease. The presence of 14-3-3η in the CSF of a patient with herpes simplex encephalitis was particularly noteworthy. This study has determined that isoform-specific 14-3-3 antibodies against β, γ, and ε should be considered for the neurochemical differentiation of CJD from other neurodegenerative diseases."],["dc.identifier.doi","10.1046/j.1471-4159.1999.0732485.x"],["dc.identifier.gro","3151688"],["dc.identifier.pmid","10582609"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8506"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.notes.submitter","chake"],["dc.relation.issn","0022-3042"],["dc.title","Isoform Pattern of 14-3-3 Proteins in the Cerebrospinal Fluid of Patients with Creutzfeldt-Jakob Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1005"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Alzheimer's Disease"],["dc.bibliographiccitation.lastpage","1015"],["dc.bibliographiccitation.volume","76"],["dc.contributor.author","Fuentes, Manuel"],["dc.contributor.author","Klostermann, Arne"],["dc.contributor.author","Kleineidam, Luca"],["dc.contributor.author","Bauer, Chris"],["dc.contributor.author","Schuchhardt, Johannes"],["dc.contributor.author","Maier, Wolfgang"],["dc.contributor.author","Jessen, Frank"],["dc.contributor.author","Frölich, Lutz"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Klöppel, Stefan"],["dc.contributor.author","Schieting, Vera"],["dc.contributor.author","Teipel, Stefan J."],["dc.contributor.author","Wagner, Michael"],["dc.contributor.author","Peters, Oliver"],["dc.date.accessioned","2021-04-14T08:27:21Z"],["dc.date.available","2021-04-14T08:27:21Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.3233/JAD-200230"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82256"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1875-8908"],["dc.relation.issn","1387-2877"],["dc.title","Identification of a Cascade of Changes in Activities of Daily Living Preceding Short-Term Clinical Deterioration in Mild Alzheimer’s Disease Dementia via Lead-Lag Analysis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","68"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Neuroscience Letters"],["dc.bibliographiccitation.lastpage","71"],["dc.bibliographiccitation.volume","440"],["dc.contributor.author","Koelsch, Heike"],["dc.contributor.author","Jessen, Frank"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Dichgans, Martin"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Froelich, Lutz"],["dc.contributor.author","Heuser, Isabella"],["dc.contributor.author","Peters, Oliver"],["dc.contributor.author","Schulz, Joerg B."],["dc.contributor.author","Schwab, Sibylle G."],["dc.contributor.author","Maier, Wolfgang"],["dc.date.accessioned","2018-11-07T11:12:54Z"],["dc.date.available","2018-11-07T11:12:54Z"],["dc.date.issued","2008"],["dc.description.abstract","SORL1 gene variants were described as risk factors of Alzheimer's disease (AD). We investigated the association of four SORL1 variants with CSF levels of A beta(42) and A beta(40) in 153 AD patients recruited from a multicenter study of the German Competence Net Dementias. Only one SORL1 SNP was associated with altered A beta(42) levels in the single marker analysis (SNP21: p = 0.011), the other SNPs did not show an association with A beta(42) orA beta(40) CSF levels. Haplotype analysis identified a three marker SORL1 haplotype consisting of SNP19 T-allele, SNP21 G-allele and SNP23 A-allele (T/G/A) which was associated with reduced A beta(42) CSF levels in AD patients (p = 0.003). A beta(40) levels were also lower in carriers of this haplotype; however, this did not reach statistical significance (p = 0.15). We found a SORL1 haplotype which was associated with CSF levels of amyloid-P cleavage products, measured as altered levels of A beta(42). Thus our data suggest that: SORL1 gene variants might influence AD pathology. (C) 2008 Elsevier Ireland Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.neulet.2008.05.049"],["dc.identifier.isi","000257640200016"],["dc.identifier.pmid","18541377"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53768"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Ireland Ltd"],["dc.relation.issn","0304-3940"],["dc.title","Influence of SORL1 gene variants: Association with CSF amyloid-beta products in probable Alzheimer's disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","466"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Fortschritte der Neurologie · Psychiatrie"],["dc.bibliographiccitation.lastpage","475"],["dc.bibliographiccitation.volume","67"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Maler, Manuel"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Bleich, Stefan"],["dc.contributor.author","Degner, Detlef"],["dc.contributor.author","Rüther, Eckart"],["dc.date.accessioned","2017-09-07T11:44:45Z"],["dc.date.available","2017-09-07T11:44:45Z"],["dc.date.issued","2008"],["dc.description.abstract","The spectrum of action of flupirtine includes analgesic, muscle-relaxant and neuroprotective properties. The substance's mechanism of action has yet to be fully explained. Over the past few years, however, evidence has accumulated that flupirtine interacts with the glutamatergic N-Methyl-D-Aspartate (NMDA) receptor. Although it was not possible to demonstrate a direct effect on the NMDA receptor, all of the findings pointed to an indirect influence on the NMDA receptor in the sense of a functional NMDA antagonism. It was thus postulated that a site of action \"up- or downstream\" of the NMDA receptor is influenced. Such a site of action proved to be the G-protein-activated inwardly rectifying K+ channels (GIRK), the opening of which leads to a stabilisation of the resting membrane potential of neuronal cells and thus causes an indirect inhibition of the NMDA receptor. At therapeutically relevant concentrations, flupirtine is a neuronal potassium channel opener. This mechanism may explain the spectrum of action of flupirtine. Selective neuronal potassium channel opening (SNEPCO) thus proves to be a new principle of action, making flupirtine the prototype of a new substance class with analgesic, muscle-relaxant and neuroprotective properties. The experimental basis for this working hypothesis and the resulting model concepts are presented from the perspective of a four-stage approach."],["dc.description.abstract","Das Wirkspektrum von Flupirtin umfaßt analgetische, muskelentspannende und neuroprotektive Eigenschaften. Der Wirkmechanismus der Substanz war bislang unzureichend bekannt. In den letzten Jahren verdichteten sich jedoch Hinweise auf eine Interaktion von Flupirtin mit dem glutamatergen N-Methyl-D-Aspartat (NMDA)-Rezeptor. Obwohl eine direkte Wirkung am NMDA-Rezeptor nicht nachweisbar war. sprachen alle Befunde für eine indirekte Beeinflussung des NMDA-Rezeptors im Sinne eines funktionellen NMDA-Antagonismus. Es wurde somit postuliert, daß ein Wirkort ,,up- oder downstream\" vom NMDA-Rezeptor beeinflußt wird. Als solcher erwiesen sich die G-Protein gesteuerten einwärts gleichrichtenden K\"-Kanale (GIRK), deren Öffnung zu einer Stabilisierung des Ruhemembranpotentials neuronaler Zellen führt und dadurch eine indirekte Hemmung des NMDA-Rezeptors bewirkt. Flupirtin ist in therapeutisch relevanten Konzentrationen ein neuronaler K'-Kanalöffner (neuronal potassium Channel opener). Dieser Mechanismus vermag das Wirkspektrum von Flupirtin zu erklären. Damit erweist sich die selektive neuronale K+-Kanaloffnung (SNEPCO) als ein neues Wirkprinzip und Flupirtin als Prototyp einer neuen Substanzklasse mit analgetischen, muskelrelaxierenden und neuroprotektiven Eigenschaften. Die experimentellen Grundlagen dieser Arbeitshypothese und der daraus resultierenden Modellvorstellungen werden in einer vierstufigen Betrachtungsebene vorgestellt."],["dc.identifier.doi","10.1055/s-2007-994997"],["dc.identifier.gro","3151740"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8561"],["dc.language.iso","de"],["dc.notes.status","final"],["dc.notes.submitter","chake"],["dc.relation.issn","0720-4299"],["dc.title","Neuronale Kaliumkanalöffnung durch Flupirtin"],["dc.title.subtitle","Opening of Neuronal K+ Channels by Flupirtine"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","857"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Journal of Neural Transmission"],["dc.bibliographiccitation.lastpage","867"],["dc.bibliographiccitation.volume","106"],["dc.contributor.author","Kornhuber, J."],["dc.contributor.author","Bleich, S."],["dc.contributor.author","Wiltfang, J."],["dc.contributor.author","Maler, M."],["dc.contributor.author","Parsons, C. G."],["dc.date.accessioned","2017-09-07T11:44:33Z"],["dc.date.available","2017-09-07T11:44:33Z"],["dc.date.issued","2002"],["dc.description.abstract","The spectrum of action of flupirtine includes analgesia, muscle relaxation and neuroprotection. N-methyl-D-aspartate (NMDA) receptor antagonism has been discussed as a possible mechanism of action of this compound with little direct evidence. The objective of the present study was to develop a plausible model to explain flupirtine's spectrum of action. A four-stage strategy was selected for this purpose: Firstly, the serum concentration of flupirtine under therapeutic conditions was determined on the basis of the current literature. The second stage involved assessing the known in-vitro effects in light of the therapeutic active concentration. Using whole cell patch clamp recordings from cultured rat superior colliculus neurones interactions between flupirtine and NMDA receptors were assessed. Only very high concentrations of flupirtine antagonized inward currents to NMDA (200 μM) at −70 mV with an lC50 against steady-state responses of 182.1 ± 12.1 μM. The effects of flupirtine were voltage-independent and not associated with receptor desensitization making actions within the NMDA receptor channel or at the glycine modulatory site unlikely. NMDA receptor antagonism probably has little relevance for the clinical efficacy of flupirtine as the concentrations needed were far higher than those achieved in clinical practice. However, the activation of a G-protein-regulated inwardly rectifying K+ channel was identified as an interesting molecular target site of flupirtine. In the next stage, the central nervous spectrum of action of experimental K+ channel openers (PCO) was considered. As far as they have been studied, experimental K+ channel openers display a spectrum of action comparable to that of flupirtine. In the final stage, a global model was developed in which flupirtine stabilizes the resting membrane potential by activating inwardly rectifying K+ channels, thus indirectly inhibiting the activation of NMDA receptors. The model presented here reconciles the known functional NMDA receptor antagonism of flupirtine with the activation of K+ channels that occurs at therapeutic concentrations, thus providing an understanding of flupirtine's spectrum of action. This makes flupirtine the prototype of a clinically applicable substance group with analgesic, muscle-relaxant and neuroprotective properties."],["dc.identifier.doi","10.1007/s007020050206"],["dc.identifier.gro","3151702"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8521"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.notes.submitter","chake"],["dc.relation.issn","0300-9564"],["dc.title","Flupirtine shows functional NMDA receptor antagonism by enhancing Mg 2+ block via activation of voltage independent potassium channels"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","547"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Alzheimer s Disease"],["dc.bibliographiccitation.lastpage","560"],["dc.bibliographiccitation.volume","49"],["dc.contributor.author","Koppara, Alexander"],["dc.contributor.author","Wolfsgruber, Steffen"],["dc.contributor.author","Kleineidam, Luca"],["dc.contributor.author","Schmidtke, Klaus"],["dc.contributor.author","Froelich, Lutz"],["dc.contributor.author","Kurz, Alexander"],["dc.contributor.author","Schulz, Stefanie"],["dc.contributor.author","Hampel, Harald"],["dc.contributor.author","Heuser, Isabella"],["dc.contributor.author","Peters, Oliver"],["dc.contributor.author","Reischies, Friedel M."],["dc.contributor.author","Jahn, Holger"],["dc.contributor.author","Luckhaus, Christian"],["dc.contributor.author","Huell, Michael"],["dc.contributor.author","Gertz, Hermann-Josef"],["dc.contributor.author","Schroeder, Johannes"],["dc.contributor.author","Pantel, Johannes"],["dc.contributor.author","Rienhoff, Otto"],["dc.contributor.author","Ruether, Eckart"],["dc.contributor.author","Henn, Fritz A."],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Maier, Wolfgang"],["dc.contributor.author","Jessen, Frank"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Wagner, Michael"],["dc.date.accessioned","2018-11-07T10:21:47Z"],["dc.date.available","2018-11-07T10:21:47Z"],["dc.date.issued","2016"],["dc.description.abstract","Background: The recently proposed latent variable delta is a new tool for dementia case finding. It is built in a structural equation modeling framework of cognitive and functional data and constitutes a novel endophenotype for Alzheimer's disease (AD) research and clinical trials. Objective: To investigate the association of delta with AD biomarkers and to compare the prediction of d with established scales for conversion to dementia in patients with mild cognitive impairment (MCI). Methods: Using data from a multicenter memory clinic study, we examined the external associations of the latent variable delta and compared delta with well-established cognitive and functional scales and cognitive-functional composite scores. For that purpose, logistic regressions with cerebrospinal fluid (CSF) biomarkers and conversion to dementia as dependent variables were performed with the investigated scores. The models were tested for significant differences. Results: In patients with MCI, delta based on a broad range of cognitive scales (including the ADAS-cog, the MMSE, and the CERAD neuropsychological battery) predicted an abnormal CSF A beta(42)/tau ratio indicative of AD (n = 340, AUC = 0.78, p < 0.001), and predicted incident dementia within 1-3 years of follow-up (n = 525, AUC= 0.84, p < 0.001). These associations were generally stronger than for any other scale or cognitive-functional composite examined. Homologs of d based on reduced test batteries yielded somewhat lower effects. Conclusion: These findings support the interpretation of d as a construct capturing the disease-related \"essence\" of cognitive and functional impairments in patients with MCI and dementia, and suggest that d might become an analytical tool for dementia research."],["dc.identifier.doi","10.3233/JAD-150257"],["dc.identifier.isi","000365710600024"],["dc.identifier.pmid","26484902"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42156"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Ios Press"],["dc.relation.issn","1875-8908"],["dc.relation.issn","1387-2877"],["dc.title","The Latent Dementia Phenotype delta is Associated with Cerebrospinal Fluid Biomarkers of Alzheimer's Disease and Predicts Conversion to Dementia in Subjects with Mild Cognitive Impairment"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]