Koch, Philipp

[["dc.bibliographiccitation.firstpage","525"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","537"],["dc.bibliographiccitation.volume","131"],["dc.contributor.author","Kumar, Sathish"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Stueber, Kathrin"],["dc.contributor.author","Wunderlich, Patrick"],["dc.contributor.author","Koch, Philipp"],["dc.contributor.author","Theil, Sandra"],["dc.contributor.author","Rezaei-Ghaleh, Nasrollah"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Bayer, Thomas A."],["dc.contributor.author","Bruestle, Oliver"],["dc.contributor.author","Thal, Dietmar Rudolf"],["dc.contributor.author","Walter, Jochen"],["dc.date.accessioned","2018-11-07T10:16:30Z"],["dc.date.available","2018-11-07T10:16:30Z"],["dc.date.issued","2016"],["dc.description.abstract","Aggregation and toxicity of the amyloid beta-peptide (A beta) are considered as critical events in the initiation and progression of Alzheimer's disease (AD). Recent evidence indicated that soluble oligomeric A beta assemblies exert pronounced toxicity, rather than larger fibrillar aggregates that deposit in the forms of extracellular plaques. While some rare mutations in the A beta sequence that cause early-onset AD promote the oligomerization, molecular mechanisms that induce the formation or stabilization of oligomers of the wild-type A beta remain unclear. Here, we identified an A beta variant phosphorylated at Ser26 residue (pSer26A beta) in transgenic mouse models of AD and in human brain that shows contrasting spatio-temporal distribution as compared to non-phosphorylated A beta (npA beta) or other modified A beta species. pSer26A beta is particularly abundant in intraneuronal deposits at very early stages of AD, but much less in extracellular plaques. pSer26A beta assembles into a specific oligomeric form that does not proceed further into larger fibrillar aggregates, and accumulates in characteristic intracellular compartments of granulovacuolar degeneration together with TDP-43 and phosphorylated tau. Importantly, pSer26A beta oligomers exert increased toxicity in human neurons as compared to other known A beta species. Thus, pSer26A beta could represent a critical species in the neurodegeneration during AD pathogenesis."],["dc.identifier.doi","10.1007/s00401-016-1546-0"],["dc.identifier.isi","000372297500003"],["dc.identifier.pmid","26898910"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13216"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41051"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1432-0533"],["dc.relation.issn","0001-6322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Phosphorylation of the amyloid beta-peptide at Ser26 stabilizes oligomeric assembly and increases neurotoxicity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]