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.firstpage","849"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Alzheimer's Disease"],["dc.bibliographiccitation.lastpage","858"],["dc.bibliographiccitation.volume","67"],["dc.contributor.author","Hornung, Karen"],["dc.contributor.author","Zampar, Silvia"],["dc.contributor.author","Engel, Nadine"],["dc.contributor.author","Klafki, Hans"],["dc.contributor.author","Liepold, Thomas"],["dc.contributor.author","Bayer, Thomas A."],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Jahn, Olaf"],["dc.contributor.author","Wirths, Oliver"],["dc.date.accessioned","2020-12-10T18:44:12Z"],["dc.date.available","2020-12-10T18:44:12Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.3233/JAD-181134"],["dc.identifier.eissn","1875-8908"],["dc.identifier.issn","1387-2877"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78365"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","N-Terminal Truncated Aβ4-42 Is a Substrate for Neprilysin Degradation in vitro and in vivo"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","101"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Alzheimer s Disease"],["dc.bibliographiccitation.lastpage","110"],["dc.bibliographiccitation.volume","49"],["dc.contributor.author","Savastano, Adriana"],["dc.contributor.author","Klafki, Hans"],["dc.contributor.author","Haussman, Ute"],["dc.contributor.author","Oberstein, Timo Jan"],["dc.contributor.author","Mueller, Petr"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Bayer, Thomas A."],["dc.date.accessioned","2018-11-07T10:21:48Z"],["dc.date.available","2018-11-07T10:21:48Z"],["dc.date.issued","2016"],["dc.description.abstract","According to the modified amyloid hypothesis, the key event in the pathogenesis of Alzheimer's disease (AD) is the deposition of neurotoxic amyloid beta-peptides (A beta s) in plaques and cerebral blood vessels. Additionally to full-length peptides, a great diversity of N-truncated A beta variants is derived from the larger amyloid-beta protein precursor (A beta PP). Vast evidence suggests that A beta(x-42) isoforms play an important role in triggering neurodegeneration due to their high abundance, amyloidogenic propensity and toxicity. Although N-truncated Ap peptides and A beta(x-42) species appear to be the crucial players in AD etiology, the A beta(2-x) isoforms did not receive much attention yet. The present study is the first to show immunohistochemical evidence of A beta(2-x) in cases of AD and its distribution in Al3PP/PS 1KI and 5XFAD transgenic mouse models using a novel antibody pAB77 that has been developed using A132-14 as antigen. Positive plaques and congophilic amyloid angiopathy (CAA) were observed in AD cases and in both mouse models. While in AD cases, abundant CAA and less pronounced plaque pathology was evident, the two mouse models showed predominantly extracellular Ap deposits and minor CAA staining. Western blotting and a capillary isoelectric focusing immunoassay demonstrated the high specificity of the antibody pAb77 against A13-variants starting with the N-terminal Alanine-2."],["dc.identifier.doi","10.3233/JAD-150394"],["dc.identifier.isi","000364409100012"],["dc.identifier.pmid","26529393"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42160"],["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","N-Truncated A beta(2-X) Starting with Position Two in Sporadic Alzheimer's Disease Cases and Two Alzheimer Mouse Models"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","101"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Alzheimer's Disease"],["dc.bibliographiccitation.lastpage","110"],["dc.bibliographiccitation.volume","49"],["dc.contributor.author","Savastano, Adriana"],["dc.contributor.author","Klafki, Hans"],["dc.contributor.author","Haußmann, Ute"],["dc.contributor.author","Oberstein, Timo Jan"],["dc.contributor.author","Muller, Petr"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Bayer, Thomas A."],["dc.date.accessioned","2017-09-07T11:44:34Z"],["dc.date.available","2017-09-07T11:44:34Z"],["dc.date.issued","2015"],["dc.description.abstract","According to the modified amyloid hypothesis, the key event in the pathogenesis of Alzheimer’s disease (AD) is the deposition of neurotoxic amyloid β-peptides (Aβs) in plaques and cerebral blood vessels. Additionally to full-length peptides, a great diversity of N-truncated Aβ variants is derived from the larger amyloid-β protein precursor (AβPP). Vast evidence suggests that Aβx-42 isoforms play an important role in triggering neurodegeneration due to their high abundance, amyloidogenic propensity and toxicity. Although N-truncated Aβ peptides and Aβx-42 species appear to be the crucial players in AD etiology, the Aβ2-X isoforms did not receive much attention yet. The present study is the first to show immunohistochemical evidence of Aβ2-X in cases of AD and its distribution in AβPP/PS1KI and 5XFAD transgenic mouse models using a novel antibody pAB77 that has been developed using Aβ2-14 as antigen. Positive plaques and congophilic amyloid angiopathy (CAA) were observed in AD cases and in both mouse models. While in AD cases, abundant CAA and less pronounced plaque pathology was evident, the two mouse models showed predominantly extracellular Aβ deposits and minor CAA staining. Western blotting and a capillary isoelectric focusing immunoassay demonstrated the high specificity of the antibody pAb77 against Aβ-variants starting with the N-terminal Alanine-2."],["dc.identifier.doi","10.3233/jad-150394"],["dc.identifier.gro","3151701"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8520"],["dc.language.iso","en"],["dc.notes.status","public"],["dc.notes.submitter","chake"],["dc.relation.issn","1387-2877"],["dc.title","N-Truncated Aβ2-X Starting with Position Two in Sporadic Alzheimer’s Disease Cases and Two Alzheimer Mouse Models"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","24"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Acta Neuropathologica Communications"],["dc.bibliographiccitation.lastpage","12"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Reinert, Jochim"],["dc.contributor.author","Richard, Bernhard C."],["dc.contributor.author","Klafki, Hans W."],["dc.contributor.author","Friedrich, Beate"],["dc.contributor.author","Bayer, Thomas A."],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Kovacs, Gabor G."],["dc.contributor.author","Ingelsson, Martin"],["dc.contributor.author","Lannfelt, Lars"],["dc.contributor.author","Paetau, Anders"],["dc.contributor.author","Bergquist, Jonas"],["dc.contributor.author","Wirths, Oliver"],["dc.date.accessioned","2017-09-07T11:44:29Z"],["dc.date.available","2017-09-07T11:44:29Z"],["dc.date.issued","2016"],["dc.description.abstract","In Alzheimer’s disease (AD) a variety of amyloid β-peptides (Aβ) are deposited in the form of extracellular diffuse and neuritic plaques (NP), as well as within the vasculature. The generation of Aβ from its precursor, the amyloid precursor protein (APP), is a highly complex procedure that involves subsequent proteolysis of APP by β- and γ-secretases. Brain accumulation of Aβ due to impaired Aβ degradation and/or altered ratios between the different Aβ species produced is believed to play a pivotal role in AD pathogenesis. While the presence of Aβ40 and Aβ42 in vascular and parenchymal amyloid have been subject of extensive studies, the deposition of carboxyterminal truncated Aβ peptides in AD has not received comparable attention. In the current study, we for the first time demonstrate the immunohistochemical localization of Aβ37 and Aβ39 in human sporadic AD (SAD). Our study further included the analysis of familial AD (FAD) cases carrying the APP mutations KM670/671NL, E693G and I716F, as well as a case of the PSEN1 ΔExon9 mutation. Aβ37 and Aβ39 were found to be widely distributed within the vasculature in the brains of the majority of studied SAD and FAD cases, the latter also presenting considerable amounts of Aβ37 containing NPs. In addition, both peptides were found to be present in extracellular plaques but only scarce within the vasculature in brains of a variety of transgenic AD mouse models. Taken together, our study indicates the importance of C-terminally truncated Aβ in sporadic and familial AD and raises questions about how these species are generated and regulated."],["dc.identifier.doi","10.1186/s40478-016-0294-7"],["dc.identifier.gro","3151681"],["dc.identifier.pmid","26955942"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12971"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8499"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","public"],["dc.notes.submitter","chake"],["dc.relation.issn","2051-5960"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Deposition of C-terminally truncated Aβ species Aβ37 and Aβ39 in Alzheimer’s disease and transgenic mouse models"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","no"],["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","96"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Fluids and Barriers of the CNS"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Klafki, Hans-Wolfgang"],["dc.contributor.author","Morgado, Barbara"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Jahn, Olaf"],["dc.contributor.author","Bauer, Chris"],["dc.contributor.author","Esselmann, Hermann"],["dc.contributor.author","Schuchhardt, Johannes"],["dc.contributor.author","Wiltfang, Jens"],["dc.date.accessioned","2022-12-05T09:15:24Z"],["dc.date.available","2022-12-05T09:15:24Z"],["dc.date.issued","2022-12-03"],["dc.date.updated","2022-12-04T04:11:01Z"],["dc.description.abstract","Abstract\r\n \r\n Background\r\n A reduced amyloid-β (Aβ)42/40 peptide ratio in blood plasma represents a peripheral biomarker of the cerebral amyloid pathology observed in Alzheimer’s disease brains. The magnitude of the measurable effect in plasma is smaller than in cerebrospinal fluid, presumably due to dilution by Aβ peptides originating from peripheral sources. We hypothesized that the observable effect in plasma can be accentuated to some extent by specifically measuring Aβ1–42 and Aβ1–40 instead of AβX–42 and AβX–40.\r\n \r\n \r\n Methods\r\n We assessed the plasma AβX–42/X–40 and Aβ1–42/1–40 ratios in an idealized clinical sample by semi-automated Aβ immunoprecipitation followed by closely related sandwich immunoassays. The amyloid-positive and amyloid-negative groups (dichotomized according to Aβ42/40 in cerebrospinal fluid) were compared regarding the median difference, mean difference, standardized effect size (Cohen’s d) and receiver operating characteristic curves. For statistical evaluation, we applied bootstrapping.\r\n \r\n \r\n Results\r\n The median Aβ1–42/1–40 ratio was 20.86% lower in amyloid-positive subjects than in the amyloid-negative group, while the median AβX–42/X–40 ratio was only 15.56% lower. The relative mean difference between amyloid-positive and amyloid-negative subjects was −18.34% for plasma Aβ1–42/1–40 compared to −15.50% for AβX–42/X–40. Cohen’s d was 1.73 for Aβ1–42/1–40 and 1.48 for plasma AβX–42/X–40. Unadjusted p-values < 0.05 were obtained after .632 bootstrapping for all three parameters. Receiver operating characteristic analysis indicated very similar areas under the curves for plasma Aβ1–42/1–40 and AβX–42/X–40.\r\n \r\n \r\n Conclusions\r\n Our findings support the hypothesis that the relatively small difference in the plasma Aβ42/40 ratio between subjects with and without evidence of brain amyloidosis can be accentuated by specifically measuring Aβ1–42/1–40 instead of AβX–42/X–40. A simplified theoretical model explaining this observation is presented."],["dc.identifier.citation","Fluids and Barriers of the CNS. 2022 Dec 03;19(1):96"],["dc.identifier.doi","10.1186/s12987-022-00390-4"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/118429"],["dc.language.iso","en"],["dc.rights","CC BY 4.0"],["dc.rights.holder","The Author(s)"],["dc.subject","Alzheimer’s disease"],["dc.subject","Biomarker"],["dc.subject","Amyloid-β peptides"],["dc.subject","Blood plasma"],["dc.subject","Aβ42/40 ratio"],["dc.subject","Immunoassay"],["dc.title","Is plasma amyloid-β 1–42/1–40 a better biomarker for Alzheimer’s disease than AβX–42/X–40?"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","80"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Alzheimer's Research & Therapy"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Walter, Susanne"],["dc.contributor.author","Kraus, Inga"],["dc.contributor.author","Klafki, Hans W."],["dc.contributor.author","Stazi, Martina"],["dc.contributor.author","Oberstein, Timo J."],["dc.contributor.author","Ghiso, Jorge"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Bayer, Thomas A."],["dc.contributor.author","Weggen, Sascha"],["dc.date.accessioned","2020-12-10T18:39:07Z"],["dc.date.available","2020-12-10T18:39:07Z"],["dc.date.issued","2017"],["dc.description.abstract","Abstract Background The deposition of neurotoxic amyloid-β (Aβ) peptides in plaques in the brain parenchyma and in cerebral blood vessels is considered to be a key event in Alzheimer’s disease (AD) pathogenesis. Although the presence and impact of full-length Aβ peptides such as Aβ1–40 and Aβ1–42 have been analyzed extensively, the deposition of N-terminally truncated Aβ peptide species has received much less attention, largely because of the lack of specific antibodies. Methods This paper describes the generation and characterization of novel antibodies selective for Aβ4–x peptides and provides immunohistochemical evidence of Aβ4–x in the human brain and its distribution in the APP/PS1KI and 5XFAD transgenic mouse models. Results The Aβ4–x staining pattern was restricted mainly to amyloid plaque cores and cerebral amyloid angiopathy in AD and Down syndrome cases and in both AD mouse models. In contrast, diffuse amyloid deposits were largely negative for Aβ4–x immunoreactivity. No overt intraneuronal staining was observed. Conclusions The findings of this study are consistent with previous reports demonstrating a high aggregation propensity of Aβ4–x peptides and suggest an important role of these N-truncated Aβ species in the process of amyloidogenesis and plaque core formation."],["dc.identifier.doi","10.1186/s13195-017-0309-z"],["dc.identifier.eissn","1758-9193"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15154"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77547"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.notes.intern","In goescholar not merged with http://resolver.sub.uni-goettingen.de/purl?gs-1/16990 but duplicate"],["dc.publisher","BioMed Central"],["dc.rights","CC BY 4.0"],["dc.rights.holder","The Author(s)."],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","N-truncated Aβ4–x peptides in sporadic Alzheimer’s disease cases and transgenic Alzheimer mouse models"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e800"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Translational Psychiatry"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Hüttenrauch, M."],["dc.contributor.author","Brauß, A."],["dc.contributor.author","Kurdakova, A."],["dc.contributor.author","Borgers, H."],["dc.contributor.author","Klinker, Florian"],["dc.contributor.author","Liebetanz, David"],["dc.contributor.author","Salinas-Riester, G."],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Klafki, Hans-Wolfgang"],["dc.contributor.author","Wirths, Oliver"],["dc.date.accessioned","2017-09-07T11:44:28Z"],["dc.date.available","2017-09-07T11:44:28Z"],["dc.date.issued","2016"],["dc.description.abstract","The evidence for a protective role of physical activity on the risk and progression of Alzheimer’s disease (AD) has been growing in the last years. Here we studied the influence of a prolonged physical and cognitive stimulation on neurodegeneration, with special emphasis on hippocampal neuron loss and associated behavioral impairment in the Tg4-42 mouse model of AD. Tg4-42 mice overexpress Aβ4-42 without any mutations, and develop an age-dependent hippocampal neuron loss associated with a severe memory decline. We demonstrate that long-term voluntary exercise diminishes CA1 neuron loss and completely rescues spatial memory deficits in different experimental settings. This was accompanied by changes in the gene expression profile of Tg4-42 mice. Deep sequencing analysis revealed an upregulation of chaperones involved in endoplasmatic reticulum protein processing, which might be intimately linked to the beneficial effects seen upon long-term exercise. We believe that we provide evidence for the first time that enhanced physical activity counteracts neuron loss and behavioral deficits in a transgenic AD mouse model. The present findings underscore the relevance of increased physical activity as a potential strategy in the prevention of dementia."],["dc.description.sponsorship","Open-Access Publikationsfonds 2016"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2016"],["dc.identifier.doi","10.1038/tp.2016.65"],["dc.identifier.gro","3151680"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13400"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8498"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.intern","In goescholar not merged with http://resolver.sub.uni-goettingen.de/purl?gs-1/14565 but duplicate"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","chake"],["dc.relation.issn","2158-3188"],["dc.rights","Goescholar"],["dc.rights.access","openAccess"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Physical activity delays hippocampal neurodegeneration and rescues memory deficits in an Alzheimer disease mouse model"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]