Bayer, Thomas A.

[["dc.bibliographiccitation.artnumber","196.e29"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Neurobiology of Aging"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Jawhar, Sadim"],["dc.contributor.author","Trawicka, Anna"],["dc.contributor.author","Jenneckens, Carolin"],["dc.contributor.author","Bayer, Thomas A."],["dc.contributor.author","Wirths, Oliver"],["dc.date.accessioned","2018-11-07T09:16:11Z"],["dc.date.available","2018-11-07T09:16:11Z"],["dc.date.issued","2012"],["dc.description.abstract","In the present report, we extend previous findings in the 5XFAD mouse model and demonstrate that these mice develop an age-dependent motor phenotype in addition to working memory deficits and reduced anxiety levels as demonstrated in an elevated plus maze task. Employing a variety of N- and C-terminal specific A beta antibodies, abundant intraneuronal and plaque-associated pathology, including accumulation of pyroglutamate A beta, was observed as early as the age of 3 months. Using unbiased stereology, we demonstrate that the 5XFAD mice develop a significant selective neuron loss in layer 5 of the cortex, leaving the overall neuron number of the total frontal cortex and hippocampus unaffected. This observation coincides with the accumulation of intraneuronal A beta peptides only in cortical Layer 5, but not in CA1, despite comparable APP expression levels. The motor phenotype correlates with abundant spinal cord pathology, as demonstrated by abundant intraneuronal A beta accumulation and extracellular plaque deposition. In addition, comparable to the APP/PS1KI mouse model, 5XFAD mice develop an age-dependent axonopathy likely contributing to the behavioral deficits. (C) 2012 IBRO All rights reserved."],["dc.identifier.doi","10.1016/j.neurobiolaging.2010.05.027"],["dc.identifier.isi","000297934700025"],["dc.identifier.pmid","20619937"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27877"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","0197-4580"],["dc.title","Motor deficits, neuron loss, and reduced anxiety coinciding with axonal degeneration and intraneuronal A beta aggregation in the 5XFAD mouse model of 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","38825"],["dc.bibliographiccitation.issue","45"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","38832"],["dc.bibliographiccitation.volume","286"],["dc.contributor.author","Jawhar, Sadim"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Bayer, Thomas A."],["dc.date.accessioned","2018-11-07T08:49:53Z"],["dc.date.available","2018-11-07T08:49:53Z"],["dc.date.issued","2011"],["dc.description.abstract","Pyroglutamate-modified amyloid-beta (A beta(pE3)) peptides are gaining considerable attention as potential key participants in the pathology of Alzheimer disease (AD) due to their abundance in AD brain, high aggregation propensity, stability, and cellular toxicity. Transgenic mice that produce high levels of A beta(pE3-42) show severe neuron loss. Recent in vitro and in vivo experiments have proven that the enzyme glutaminyl cyclase catalyzes the formation of A beta(pE3).In this minireview, we summarize the current knowledge on A beta(pE3), discussing its discovery, biochemical properties, molecular events determining formation, prevalence in the brains of AD patients, Alzheimer mouse models, and potential as a target for therapy and as a diagnostic marker."],["dc.identifier.doi","10.1074/jbc.R111.288308"],["dc.identifier.isi","000296759800001"],["dc.identifier.pmid","21965666"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21563"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","0021-9258"],["dc.title","Pyroglutamate Amyloid-beta (A beta): A Hatchet Man in Alzheimer Disease"],["dc.type","review"],["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","4454"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","4460"],["dc.bibliographiccitation.volume","286"],["dc.contributor.author","Jawhar, Sadim"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Schilling, Stephan"],["dc.contributor.author","Graubner, Sigrid"],["dc.contributor.author","Demuth, Hans-Ulrich"],["dc.contributor.author","Bayer, Thomas A."],["dc.date.accessioned","2021-06-01T10:51:07Z"],["dc.date.available","2021-06-01T10:51:07Z"],["dc.date.issued","2011"],["dc.identifier.doi","10.1074/jbc.M110.185819"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86895"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.issn","0021-9258"],["dc.title","Overexpression of Glutaminyl Cyclase, the Enzyme Responsible for Pyroglutamate Aβ Formation, Induces Behavioral Deficits, and Glutaminyl Cyclase Knock-out Rescues the Behavioral Phenotype in 5XFAD Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","96"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Neurobiology of Aging"],["dc.bibliographiccitation.lastpage","107"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Cotel, Marie-Caroline"],["dc.contributor.author","Jawhar, Sadim"],["dc.contributor.author","Christensen, Ditte Zerlang"],["dc.contributor.author","Bayer, Thomas A."],["dc.contributor.author","Wirths, Oliver"],["dc.date.accessioned","2018-11-07T09:16:11Z"],["dc.date.available","2018-11-07T09:16:11Z"],["dc.date.issued","2012"],["dc.description.abstract","Environmental enrichment has been used in a variety of transgenic mouse models of Alzheimer's disease (AD), however, with conflicting results. Here we studied the influence of environmental enrichment in a severely affected AD mouse model, showing a multiplicity of pathological alterations including hippocampal neuron loss. APP/PS1KI and wild type (WT) control mice were housed under standard conditions or in enriched cages equipped with various objects and running wheels. Amyloid plaque load, motor and working memory performance, axonopathy, as well as CA1 neuron number and hippocampal neurogenesis were assessed. Although a partial improvement in motor performance was observed, 4 months of enriched housing showed no beneficial effects in terms of working memory, A beta plaque pathology, or neuron loss in APP/PS1KI mice. In addition, no changes in hippocampal neurogenesis and even an aggravation of the axonal phenotype were detected with a tendency toward a premature death. The APP/PS1KI model represents a model for mild to severe AD showing early behavioral deficits starting at 2 months of age with fast deterioration. Therefore our data might suggest that physical activity and enriched environment might be more beneficial in patients with mild cognitive impairment than in patients with incipient AD. (C) 2012 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.neurobiolaging.2010.02.012"],["dc.identifier.isi","000297934700010"],["dc.identifier.pmid","20359774"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27876"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","1558-1497"],["dc.relation.issn","0197-4580"],["dc.title","Environmental enrichment fails to rescue working memory deficits, neuron loss, and neurogenesis in APP/PS1KI mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]