Klafki, Hans-Wolfgang

[["dc.bibliographiccitation.firstpage","6564"],["dc.bibliographiccitation.issue","18"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","21"],["dc.contributor.affiliation","Klafki, Hans W.; \t\t \r\n\t\t Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, D37075 Göttingen, Germany, hans.klafki@med.uni-goettingen.de"],["dc.contributor.affiliation","Rieper, Petra; \t\t \r\n\t\t Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, D37075 Göttingen, Germany, petra.rieper@med.uni-goettingen.de"],["dc.contributor.affiliation","Matzen, Anja; \t\t \r\n\t\t IBL International GmbH, Tecan Group Company, D-22335 Hamburg, Germany, Anja.Matzen@tecan.com"],["dc.contributor.affiliation","Zampar, Silvia; \t\t \r\n\t\t Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, D37075 Göttingen, Germany, silvia.zampar@med.uni-goettingen.de"],["dc.contributor.affiliation","Wirths, Oliver; \t\t \r\n\t\t Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, D37075 Göttingen, Germany, oliver.wirths@medizin.uni-goettingen.de"],["dc.contributor.affiliation","Vogelgsang, Jonathan; \t\t \r\n\t\t Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, D37075 Göttingen, Germany, jonathan.vogelgsang@med.uni-goettingen.de"],["dc.contributor.affiliation","Osterloh, Dirk; \t\t \r\n\t\t Roboscreen GmbH, D-04129 Leipzig, Germany, dirk.osterloh@roboscreen.com"],["dc.contributor.affiliation","Rohdenburg, Lara; \t\t \r\n\t\t Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, D37075 Göttingen, Germany, lara.rohdenburg@stud.uni-goettingen.de"],["dc.contributor.affiliation","Oberstein, Timo J.; \t\t \r\n\t\t Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, D-91054 Erlangen, Germany, Timo.Oberstein@uk-erlangen.de"],["dc.contributor.affiliation","Jahn, Olaf; \t\t \r\n\t\t Max-Planck-Institute of Experimental Medicine, Proteomics Group, D-37075 Göttingen, Germany, jahn@em.mpg.de"],["dc.contributor.affiliation","Beyer, Isaak; \t\t \r\n\t\t Faculty of Chemistry, Technische Universität Dresden, D-01069 Dresden, Germany, isaak.beyer@web.de"],["dc.contributor.affiliation","Lachmann, Ingolf; \t\t \r\n\t\t Roboscreen GmbH, D-04129 Leipzig, Germany, ingolf.lachmann@roboscreen.com"],["dc.contributor.affiliation","Knölker, Hans-Joachim; \t\t \r\n\t\t Faculty of Chemistry, Technische Universität Dresden, D-01069 Dresden, Germany, hans-joachim.knoelker@tu-dresden.de"],["dc.contributor.affiliation","Wiltfang, Jens; \t\t \r\n\t\t Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, D37075 Göttingen, Germany, Jens.Wiltfang@med.uni-goettingen.de\t\t \r\n\t\t German Center for Neurodegenerative Diseases (DZNE), D-37075 Göttingen, Germany, Jens.Wiltfang@med.uni-goettingen.de\t\t \r\n\t\t Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal, Jens.Wiltfang@med.uni-goettingen.de"],["dc.contributor.author","Klafki, Hans W."],["dc.contributor.author","Rieper, Petra"],["dc.contributor.author","Matzen, Anja"],["dc.contributor.author","Zampar, Silvia"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Vogelgsang, Jonathan"],["dc.contributor.author","Osterloh, Dirk"],["dc.contributor.author","Rohdenburg, Lara"],["dc.contributor.author","Oberstein, Timo J."],["dc.contributor.author","Jahn, Olaf"],["dc.contributor.author","Beyer, Isaak"],["dc.contributor.author","Lachmann, Ingolf"],["dc.contributor.author","Knölker, Hans-Joachim"],["dc.contributor.author","Wiltfang, Jens"],["dc.date.accessioned","2021-04-14T08:32:33Z"],["dc.date.available","2021-04-14T08:32:33Z"],["dc.date.issued","2020"],["dc.date.updated","2022-09-06T16:24:24Z"],["dc.identifier.doi","10.3390/ijms21186564"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17555"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83948"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","1422-0067"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Development and Technical Validation of an Immunoassay for the Detection of APP669–711 (Aβ−3–40) in Biological Samples"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","94"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Alzheimer's Research & Therapy"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Aichholzer, Freyja"],["dc.contributor.author","Klafki, Hans-Wolfgang"],["dc.contributor.author","Ogorek, Isabella"],["dc.contributor.author","Vogelgsang, Jonathan"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Scherbaum, Norbert"],["dc.contributor.author","Weggen, Sascha"],["dc.contributor.author","Wirths, Oliver"],["dc.date.accessioned","2021-11-25T11:07:12Z"],["dc.date.accessioned","2022-08-18T12:39:08Z"],["dc.date.available","2021-11-25T11:07:12Z"],["dc.date.available","2022-08-18T12:39:08Z"],["dc.date.issued","2021-05-04"],["dc.date.updated","2022-07-29T12:17:48Z"],["dc.description.abstract","Abstract\r\n \r\n Background\r\n Alzheimer’s disease (AD) is a neurodegenerative disorder associated with extracellular amyloid-β peptide deposition and progressive neuron loss. Strong evidence supports that neuroinflammatory changes such as the activation of astrocytes and microglia cells are important in the disease process. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a transmembrane glycoprotein that has recently been associated with an emerging role in neuroinflammation, which has been reported to be increased in post-mortem brain samples from AD and Parkinson’s disease patients.\r\n \r\n \r\n Methods\r\n The present study describes the partial “fit for purpose” validation of a commercially available immunoassay for the determination of GPNMB levels in the cerebrospinal fluid (CSF). We further assessed the applicability of GPNMB as a potential biomarker for AD in two different cohorts that were defined by biomarker-supported clinical diagnosis or by neuroimaging with amyloid positron emission tomography, respectively.\r\n \r\n \r\n Results\r\n The results indicated that CSF GPNMB levels could not distinguish between AD or controls with other neurological diseases but correlated with other parameters such as aging and CSF pTau levels.\r\n \r\n \r\n Conclusions\r\n The findings of this study do not support GPNMB in CSF as a valuable neurochemical diagnostic biomarker of AD but warrant further studies employing healthy control individuals."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.citation","Alzheimer's Research & Therapy. 2021 May 04;13(1):94"],["dc.identifier.doi","10.1186/s13195-021-00828-1"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/93530"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112967"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.publisher","BioMed Central"],["dc.relation.eissn","1758-9193"],["dc.rights","CC BY 4.0"],["dc.rights.holder","The Author(s)"],["dc.subject","Alzheimer’s disease"],["dc.subject","GPNMB"],["dc.subject","Cerebrospinal fluid"],["dc.subject","Biomarker"],["dc.subject","Inflammation"],["dc.subject","Immunoassay"],["dc.title","Evaluation of cerebrospinal fluid glycoprotein NMB (GPNMB) as a potential biomarker for Alzheimer’s disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","121"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Alzheimer's Research & Therapy"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Shahpasand-Kroner, Hedieh"],["dc.contributor.author","Klafki, Hans-W."],["dc.contributor.author","Bauer, Chris"],["dc.contributor.author","Schuchhardt, Johannes"],["dc.contributor.author","Hüttenrauch, Melanie"],["dc.contributor.author","Stazi, Martina"],["dc.contributor.author","Bouter, Caroline"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Vogelgsang, Jonathan"],["dc.contributor.author","Wiltfang, Jens"],["dc.date.accessioned","2019-07-09T11:49:37Z"],["dc.date.available","2019-07-09T11:49:37Z"],["dc.date.issued","2018"],["dc.description.abstract","Abstract Background The quantification of amyloid-beta (Aβ) peptides in blood plasma as potential biomarkers of Alzheimer’s disease (AD) is hampered by very low Aβ concentrations and the presence of matrix components that may interfere with the measurements. Methods We developed a two-step immunoassay for the simultaneous measurement of the relative levels of Aβ38, Aβ40 and Aβ42 in human EDTA plasma. The assay was employed for the study of 23 patients with dementia of the Alzheimer’s type (AD-D) and 17 patients with dementia due to other reasons (OD). We examined relationships with the clinical diagnosis, cerebral Aβ load as quantified by amyloid-positron emission tomography, apolipoprotein E genotype, Aβ levels and Tau protein in cerebrospinal fluid. Results Preconcentration of plasma Aβ peptides by immunoprecipitation substantially facilitated their immunological measurements. The Aβ42/Aβ40 and Aβ42/Aβ38 ratios were statistically significantly lower in the AD-D patients than in the OD group. The areas under the receiver operating characteristic curves reached 0.87 for the Aβ42/Aβ40 ratio and 0.80 for the Aβ42/Aβ38 ratio. Conclusions The measurement of plasma Aβ peptides with an immunological assay can be improved by preconcentration via immunoprecipitation with an antibody against the Aβ amino-terminus and elution of the captured peptides by heating in a mild detergent-containing buffer. Our findings support the Aβ42/Aβ40 ratio in blood plasma as a promising AD biomarker candidate which correlates significantly with the validated core biomarkers of AD. Further studies will be needed for technical advancement of the assay and validation of the biomarker findings."],["dc.identifier.doi","10.1186/s13195-018-0448-x"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15726"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59592"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","BioMed Central"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","A two-step immunoassay for the simultaneous assessment of Aβ38, Aβ40 and Aβ42 in human blood plasma supports the Aβ42/Aβ40 ratio as a promising biomarker candidate of Alzheimer’s disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","127"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Alzheimer's Research & Therapy"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Klafki, Hans-W."],["dc.contributor.author","Vogelgsang, Jonathan"],["dc.contributor.author","Manuilova, Ekaterina"],["dc.contributor.author","Bauer, Chris"],["dc.contributor.author","Jethwa, Alexander"],["dc.contributor.author","Esselmann, Hermann"],["dc.contributor.author","Jahn-Brodmann, Anke"],["dc.contributor.author","Osterloh, Dirk"],["dc.contributor.author","Lachmann, Ingolf"],["dc.contributor.author","Breitling, Benedict"],["dc.contributor.author","Rauter, Carolin"],["dc.contributor.author","Hansen, Niels"],["dc.contributor.author","Bouter, Caroline"],["dc.contributor.author","Palme, Stefan"],["dc.contributor.author","Schuchhardt, Johannes"],["dc.contributor.author","Wiltfang, Jens"],["dc.date.accessioned","2022-09-12T07:56:44Z"],["dc.date.available","2022-09-12T07:56:44Z"],["dc.date.issued","2022-09-07"],["dc.date.updated","2022-09-11T03:10:27Z"],["dc.description.abstract","Abstract\r\n \r\n Background\r\n Measurements of the amyloid-β (Aβ) 42/40 ratio in blood plasma may support the early diagnosis of Alzheimer’s disease and aid in the selection of suitable participants in clinical trials. Here, we compared the diagnostic performance of fully automated prototype plasma Aβ42/40 assays with and without pre-analytical sample workup by immunoprecipitation.\r\n \r\n \r\n Methods\r\n A pre-selected clinical sample comprising 42 subjects with normal and 38 subjects with low cerebrospinal fluid (CSF) Aβ42/40 ratios was studied. The plasma Aβ42/40 ratios were determined with fully automated prototype Elecsys® immunoassays (Roche Diagnostics GmbH, Penzberg, Germany) by direct measurements in EDTA plasma or after pre-analytical Aβ immunoprecipitation. The diagnostic performance for the detection of abnormal CSF Aβ42/40 was analyzed by receiver operating characteristic (ROC) analysis. In an additional post hoc analysis, a biomarker-supported clinical diagnosis was used as a second endpoint.\r\n \r\n \r\n Results\r\n Pre-analytical immunoprecipitation resulted in a significant increase in the area under the ROC curve (AUC) from 0.73 to 0.88 (p = 0.01547) for identifying subjects with abnormal CSF Aβ42/40. A similar improvement in the diagnostic performance by pre-analytical immunoprecipitation was also observed when a biomarker-supported clinical diagnosis was used as a second endpoint (AUC increase from 0.77 to 0.92, p = 0.01576).\r\n \r\n \r\n Conclusions\r\n Our preliminary observations indicate that pre-analytical Aβ immunoprecipitation can improve the diagnostic performance of plasma Aβ assays for detecting brain amyloid pathology. The findings may aid in the further development of blood-based immunoassays for Alzheimer’s disease ultimately suitable for screening and routine use."],["dc.identifier.citation","Alzheimer's Research & Therapy. 2022 Sep 07;14(1):127"],["dc.identifier.doi","10.1186/s13195-022-01071-y"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/114202"],["dc.language.iso","en"],["dc.rights","CC BY 4.0"],["dc.rights.holder","The Author(s)"],["dc.subject","Alzheimer’s disease"],["dc.subject","Biomarker assay"],["dc.subject","Plasma Amyloid-β 42/40"],["dc.subject","Immunoprecipitation"],["dc.subject","Pre-analytical sample workup"],["dc.title","Diagnostic performance of automated plasma amyloid-β assays combined with pre-analytical immunoprecipitation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","578"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","589"],["dc.bibliographiccitation.volume","160"],["dc.contributor.affiliation","Wirths, Oliver; 1\r\nDepartment of Psychiatry and Psychotherapy\r\nUniversity Medical Center Goettingen (UMG)\r\nGeorg‐August‐University\r\nGoettingen Germany"],["dc.contributor.affiliation","Mollenhauer, Brit; 2\r\nDepartment of Neurology\r\nUniversity Medical Center Goettingen (UMG)\r\nGeorg‐August‐University\r\nGoettingen Germany"],["dc.contributor.affiliation","Liepold, Thomas; 4\r\nMax Planck Institute of Experimental Medicine\r\nProteomics Group\r\nGoettingen Germany"],["dc.contributor.affiliation","Rieper, Petra; 1\r\nDepartment of Psychiatry and Psychotherapy\r\nUniversity Medical Center Goettingen (UMG)\r\nGeorg‐August‐University\r\nGoettingen Germany"],["dc.contributor.affiliation","Esselmann, Hermann; 1\r\nDepartment of Psychiatry and Psychotherapy\r\nUniversity Medical Center Goettingen (UMG)\r\nGeorg‐August‐University\r\nGoettingen Germany"],["dc.contributor.affiliation","Vogelgsang, Jonathan; 1\r\nDepartment of Psychiatry and Psychotherapy\r\nUniversity Medical Center Goettingen (UMG)\r\nGeorg‐August‐University\r\nGoettingen Germany"],["dc.contributor.affiliation","Wiltfang, Jens; 1\r\nDepartment of Psychiatry and Psychotherapy\r\nUniversity Medical Center Goettingen (UMG)\r\nGeorg‐August‐University\r\nGoettingen Germany"],["dc.contributor.author","Klafki, Hans‐Wolfgang"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Liepold, Thomas"],["dc.contributor.author","Rieper, Petra"],["dc.contributor.author","Esselmann, Hermann"],["dc.contributor.author","Vogelgsang, Jonathan"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Jahn, Olaf"],["dc.date.accessioned","2022-02-01T10:31:26Z"],["dc.date.available","2022-02-01T10:31:26Z"],["dc.date.issued","2022"],["dc.date.updated","2022-06-15T00:17:43Z"],["dc.description.abstract","Abstract Neurochemical biomarkers can support the diagnosis of Alzheimer’s disease and may facilitate clinical trials. In blood plasma, the ratio of the amyloid‐β (Aβ) peptides Aβ−3–40/Aβ1–42 can predict cerebral amyloid‐β pathology with high accuracy (Nakamura et al., 2018). Whether or not Aβ−3–40 (aka. amyloid precursor protein (APP) 669–711) is also present in cerebrospinal fluid (CSF) is not clear. Here, we investigated whether Aβ−3–40 can be detected in CSF and to what extent the CSF Aβ−3–40/Aβ42 ratio is able to differentiate between individuals with or without amyloid‐β positron emission tomography (PET) evidence of brain amyloid. The occurrence of Aβ−3–40 in human CSF was assessed by immunoprecipitation followed by mass spectrometry. For quantifying the CSF concentrations of Aβ−3–40 in 23 amyloid PET‐negative and 17 amyloid PET‐positive subjects, we applied a sandwich‐type immunoassay. Our findings provide clear evidence of the presence of Aβ−3–40 and Aβ−3–38 in human CSF. While there was no statistically significant difference in the CSF concentration of Aβ−3–40 between the two diagnostic groups, the CSF Aβ−3–40/Aβ42 ratio was increased in the amyloid PET‐positive individuals. We conclude that Aβ−3–40 appears to be a regular constituent of CSF and may potentially serve to accentuate the selective decrease in CSF Aβ42 in Alzheimer's disease. image"],["dc.description.abstract","Cerebral amyloid‐β pathology can be predicted by the Aβ−3–40/Aβ1–42 peptide ratio in blood plasma (Nakamura et al., 2018, Nature 554, 249). However, it is still unclear whether Aβ−3–x peptides occur in cerebrospinal fluid (CSF). By immunoprecipitation‐mass spectrometry (IP‐MS), we show that Aβ−3–40 and Aβ−3–38 are regular constituents of CSF. The CSF Aβ−3–40/Aβ42 ratio, measured with a sandwich immunoassay, was found to be increased in individuals with positron emission tomography (PET) evidence of brain amyloid. Thus, CSF Aβ−3–40 may serve to accentuate the selective decrease in CSF Aβ42 in Alzheimer's disease. image"],["dc.identifier.doi","10.1111/jnc.15571"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/98861"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-517"],["dc.relation.eissn","1471-4159"],["dc.relation.issn","0022-3042"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes."],["dc.rights.uri","http://creativecommons.org/licenses/by-nc/4.0/"],["dc.title","Detection and quantification of Aβ−3–40 (APP669‐711) in cerebrospinal fluid"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]