Saiepour, Nasrin

[["dc.bibliographiccitation.artnumber","56"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Acta Neuropathologica Communications"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","Antonios, Gregory"],["dc.contributor.author","Saiepour, Nasrin"],["dc.contributor.author","Bouter, Yvonne"],["dc.contributor.author","Richard, Bernhard C."],["dc.contributor.author","Paetau, Anders"],["dc.contributor.author","Verkkoniemi-Ahola, Auli"],["dc.contributor.author","Lannfelt, Lars"],["dc.contributor.author","Ingelsson, Martin"],["dc.contributor.author","Kovacs, Gabor G."],["dc.contributor.author","Pillot, Thierry"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Bayer, Thomas A."],["dc.date.accessioned","2019-07-09T11:41:53Z"],["dc.date.available","2019-07-09T11:41:53Z"],["dc.date.issued","2013"],["dc.description.abstract","Abstract Background The amyloid hypothesis in Alzheimer disease (AD) considers amyloid β peptide (Aβ) deposition causative in triggering down-stream events like neurofibrillary tangles, cell loss, vascular damage and memory decline. In the past years N-truncated Aβ peptides especially N-truncated pyroglutamate AβpE3-42 have been extensively studied. Together with full-length Aβ1–42 and Aβ1–40, N-truncated AβpE3-42 and Aβ4–42 are major variants in AD brain. Although Aβ4–42 has been known for a much longer time, there is a lack of studies addressing the question whether AβpE3-42 or Aβ4–42 may precede the other in Alzheimer’s disease pathology. Results Using different Aβ antibodies specific for the different N-termini of N-truncated Aβ, we discovered that Aβ4-x preceded AβpE3-x intraneuronal accumulation in a transgenic mouse model for AD prior to plaque formation. The novel Aβ4-x immunoreactive antibody NT4X-167 detected high molecular weight aggregates derived from N-truncated Aβ species. While NT4X-167 significantly rescued Aβ4–42 toxicity in vitro no beneficial effect was observed against Aβ1–42 or AβpE3-42 toxicity. Phenylalanine at position four of Aβ was imperative for antibody binding, because its replacement with alanine or proline completely prevented binding. Although amyloid plaques were observed using NT4X-167 in 5XFAD transgenic mice, it barely reacted with plaques in the brain of sporadic AD patients and familial cases with the Arctic, Swedish and the presenilin-1 PS1Δ9 mutation. A consistent staining was observed in blood vessels in all AD cases with cerebral amyloid angiopathy. There was no cross-reactivity with other aggregates typical for other common neurodegenerative diseases showing that NT4X-167 staining is specific for AD. Conclusions Aβ4-x precedes AβpE3-x in the well accepted 5XFAD AD mouse model underlining the significance of N-truncated species in AD pathology. NT4X-167 therefore is the first antibody reacting with Aβ4-x and represents a novel tool in Alzheimer research."],["dc.identifier.doi","10.1186/2051-5960-1-56"],["dc.identifier.pmid","24252153"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12500"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58537"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","N-truncated Abeta starting with position four: early intraneuronal accumulation and rescue of toxicity using NT4X-167, a novel monoclonal antibody"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]