Wirths, Oliver

[["dc.bibliographiccitation.firstpage","871"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of Alzheimer s Disease"],["dc.bibliographiccitation.lastpage","881"],["dc.bibliographiccitation.volume","39"],["dc.contributor.author","Reinert, Jochim"],["dc.contributor.author","Martens, Henrik"],["dc.contributor.author","Huettenrauch, Melanie"],["dc.contributor.author","Kolbow, Tekla"],["dc.contributor.author","Lannfelt, Lars"],["dc.contributor.author","Ingelsson, Martin"],["dc.contributor.author","Paetau, Anders"],["dc.contributor.author","Verkkoniemi-Ahola, Auli"],["dc.contributor.author","Bayer, Thomas A."],["dc.contributor.author","Wirths, Oliver"],["dc.date.accessioned","2018-11-07T09:46:32Z"],["dc.date.available","2018-11-07T09:46:32Z"],["dc.date.issued","2014"],["dc.description.abstract","The pathogenesis of Alzheimer's disease (AD) is believed to be closely dependent on deposits of neurotoxic amyloid-beta peptides (A beta), which become abundantly present throughout the central nervous system in advanced stages of the disease. The different A beta peptides existing are generated by subsequent cleavage of the amyloid-beta protein precursor (A beta PP) and may vary in length and differ at their C-terminus. Despite extensive studies on the most prevalent species A beta(40) and A beta(42), A beta peptides with other C-termini such as A beta(38) have not received much attention. In the present study, we used a highly specific and sensitive antibody against A beta(38) to analyze the distribution of this A beta species in cases of sporadic and familial AD, as well as in the brains of a series of established transgenic AD mouse models. We found A beta(38) to be present as vascular deposits in the brains of the majority of sporadic AD cases, whereas it is largely absent in non-demented control cases. A beta(38)-positive extracellular plaques were virtually limited to familial cases. Interestingly we observed A beta(38)-positive plaques not only among familial cases due to A beta PP mutations, but also in cases of familial AD caused by presenilin (PSEN) mutations. Furthermore we demonstrate that A beta(38) deposits in the form of extracellular plaques are common in several AD transgenic mouse models carrying either only A beta PP, or combinations of A beta PP, PSEN1, and tau transgenes."],["dc.identifier.doi","10.3233/JAD-131373"],["dc.identifier.isi","000331842500017"],["dc.identifier.pmid","24305500"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34892"],["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","A beta(38) in the Brains of Patients with Sporadic and Familial Alzheimer's Disease and Transgenic 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","41517"],["dc.bibliographiccitation.issue","53"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","41524"],["dc.bibliographiccitation.volume","285"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Erck, Christian"],["dc.contributor.author","Martens, Henrik"],["dc.contributor.author","Harmeier, Anja"],["dc.contributor.author","Geumann, Constanze"],["dc.contributor.author","Jawhar, Sadim"],["dc.contributor.author","Kumar, Sathish"],["dc.contributor.author","Multhaup, Gerd"],["dc.contributor.author","Walter, Jochen"],["dc.contributor.author","Ingelsson, Martin"],["dc.contributor.author","Degerman-Gunnarsson, Malin"],["dc.contributor.author","Kalimo, Hannu"],["dc.contributor.author","Huitinga, Inge"],["dc.contributor.author","Lannfelt, Lars"],["dc.contributor.author","Bayer, Thomas A."],["dc.date.accessioned","2018-11-07T08:35:44Z"],["dc.date.available","2018-11-07T08:35:44Z"],["dc.date.issued","2010"],["dc.description.abstract","N-terminally truncated A beta peptides starting with pyroglutamate (A beta pE3) represent a major fraction of all A beta peptides in the brain of Alzheimer disease (AD) patients. A beta pE3 has a higher aggregation propensity and stability and shows increased toxicity compared with full-length A beta. In the present work, we generated a novel monoclonal antibody (9D5) that selectively recognizes oligomeric assemblies of A beta pE3 and studied the potential involvement of oligomeric A beta pE3 in vivo using transgenic mouse models as well as human brains from sporadic and familial AD cases. 9D5 showed an unusual staining pattern with almost nondetectable plaques in sporadic AD patients and non-demented controls. Interestingly, in sporadic and familial AD cases prominent intraneuronal and blood vessel staining was observed. Using a novel sandwich ELISA significantly decreased levels of oligomers in plasma samples from patients with AD compared with healthy controls were identified. Moreover, passive immunization of 5XFAD mice with 9D5 significantly reduced overall A beta plaque load and A beta pE3 levels, and normalized behavioral deficits. These data indicate that 9D5 is a therapeutically and diagnostically effective monoclonal antibody targeting low molecular weight A beta pE3 oligomers."],["dc.description.sponsorship","German Federal Ministry for Economy; Fritz Thyssen Stiftung"],["dc.identifier.doi","10.1074/jbc.M110.178707"],["dc.identifier.isi","000285622600038"],["dc.identifier.pmid","20971852"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18145"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","0021-9258"],["dc.title","Identification of Low Molecular Weight Pyroglutamate A beta Oligomers in Alzheimer Disease A NOVEL TOOL FOR THERAPY AND DIAGNOSIS"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1379"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Neurobiology of Aging"],["dc.bibliographiccitation.lastpage","1387"],["dc.bibliographiccitation.volume","32"],["dc.contributor.author","Marcello, Andrea"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Schneider-Axmann, Thomas"],["dc.contributor.author","Degerman-Gunnarsson, Malin"],["dc.contributor.author","Lannfelt, Lars"],["dc.contributor.author","Bayer, Thomas A."],["dc.date.accessioned","2021-06-01T10:49:48Z"],["dc.date.available","2021-06-01T10:49:48Z"],["dc.date.issued","2011"],["dc.identifier.doi","10.1016/j.neurobiolaging.2009.08.011"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86420"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.issn","0197-4580"],["dc.title","Reduced levels of IgM autoantibodies against N-truncated pyroglutamate Aβ in plasma of patients with Alzheimer's disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]