Bayer, Thomas A.

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Acta neuropathologica communications"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","Kalimo, Hannu"],["dc.contributor.author","Lalowski, Maciej"],["dc.contributor.author","Bogdanovic, Nenad"],["dc.contributor.author","Philipson, Ola"],["dc.contributor.author","Bird, Thomas D."],["dc.contributor.author","Nochlin, David"],["dc.contributor.author","Schellenberg, Gerard D."],["dc.contributor.author","Brundin, Rosemarie"],["dc.contributor.author","Olofsson, Tommie"],["dc.contributor.author","Soliymani, Rabah"],["dc.contributor.author","Baumann, Marc"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Bayer, Thomas A."],["dc.contributor.author","Nilsson, Lars"],["dc.contributor.author","Basun, Hans"],["dc.contributor.author","Lannfelt, Lars"],["dc.contributor.author","Ingelsson, Martin"],["dc.date.accessioned","2019-07-09T11:42:19Z"],["dc.date.available","2019-07-09T11:42:19Z"],["dc.date.issued","2013"],["dc.description.abstract","BACKGROUND: The Arctic mutation (p.E693G/p.E22G)fs within the β-amyloid (Aβ) region of the β-amyloid precursor protein gene causes an autosomal dominant disease with clinical picture of typical Alzheimer's disease. Here we report the special character of Arctic AD neuropathology in four deceased patients. RESULTS: Aβ deposition in the brains was wide-spread (Thal phase 5) and profuse. Virtually all parenchymal deposits were composed of non-fibrillar, Congo red negative Aβ aggregates. Congo red only stained angiopathic vessels. Mass spectrometric analyses showed that Aβ deposits contained variably truncated and modified wild type and mutated Aβ species. In three of four Arctic AD brains, most cerebral cortical plaques appeared targetoid with centres containing C-terminally (beyond aa 40) and variably N-terminally truncated Aβ surrounded by coronas immunopositive for Aβx-42. In the fourth patient plaque centres contained almost no Aβ making the plaques ring-shaped. The architectural pattern of plaques also varied between different anatomic regions. Tau pathology corresponded to Braak stage VI, and appeared mainly as delicate neuropil threads (NT) enriched within Aβ plaques. Dystrophic neurites were scarce, while neurofibrillary tangles were relatively common. Neuronal perikarya within the Aβ plaques appeared relatively intact. CONCLUSIONS: In Arctic AD brain differentially truncated abundant Aβ is deposited in plaques of variable numbers and shapes in different regions of the brain (including exceptional targetoid plaques in neocortex). The extracellular non-fibrillar Aβ does not seem to cause overt damage to adjacent neurons or to induce formation of neurofibrillary tangles, supporting the view that intracellular Aβ oligomers are more neurotoxic than extracellular Aβ deposits. However, the enrichment of NTs within plaques suggests some degree of intra-plaque axonal damage including accumulation of hp-tau, which may impair axoplasmic transport, and thereby contribute to synaptic loss. Finally, similarly as the cotton wool plaques in AD resulting from exon 9 deletion in the presenilin-1 gene, the Arctic plaques induced only modest glial and inflammatory tissue reaction."],["dc.identifier.doi","10.1186/2051-5960-1-60"],["dc.identifier.fs","599195"],["dc.identifier.pmid","24252272"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58642"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2051-5960"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","The Arctic AβPP mutation leads to Alzheimer's disease pathology with highly variable topographic deposition of differentially truncated Aβ."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["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.firstpage","913"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Journal of Neural Transmission"],["dc.bibliographiccitation.lastpage","920"],["dc.bibliographiccitation.volume","116"],["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"],["dc.date.accessioned","2019-07-09T11:52:23Z"],["dc.date.available","2019-07-09T11:52:23Z"],["dc.date.issued","2009"],["dc.description.abstract","It has previously been shown that immune complexes (IC) of a given biomarker with class M immunoglobulins (IgM) provide better performances compared to the unbound biomarker in a number of cancer entities. In the present work, we investigated IC of IgM-Aβ as a potential biomarker for Alzheimer’s disease (AD). Aβ–IgM concentration has been measured in 75 plasma samples from patients with AD, individuals with mild cognitive impairment (MCI), and healthy age- and sex-matched controls (HC). To characterize the fractions associated with Aβ, pooled plasma samples were subjected to gel-filtration analysis. Size-separated fractions were analyzed for the presence of Aβ using a sandwich ELIp. assay. A strong reactivity was observed in the high molecular weight IgM (>500 kDa) and 150 kDa (IgG) fractions indicating that blood Aβ is strongly associated with antibodies. Using an ELISA assay detecting Aβ–IgM complexes, we observed that high levels of Aβ–IgMs were detectable in HC and MCI patients; however, there was no significant difference to the AD group."],["dc.identifier.doi","10.1007/s00702-009-0224-y"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?goescholar/3557"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60171"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Springer"],["dc.publisher.place","Vienna"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Circulating immune complexes of Aβ and IgM in plasma of patients with Alzheimer’s disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["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"]]

[["dc.bibliographiccitation.firstpage","85"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Neural Transmission"],["dc.bibliographiccitation.lastpage","96"],["dc.bibliographiccitation.volume","117"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Bethge, Tobias"],["dc.contributor.author","Marcello, Andrea"],["dc.contributor.author","Harmeier, Anja"],["dc.contributor.author","Jawhar, Sadim"],["dc.contributor.author","Lucassen, Paul J."],["dc.contributor.author","Multhaup, Gerd"],["dc.contributor.author","Brody, David L."],["dc.contributor.author","Esparza, Thomas"],["dc.contributor.author","Ingelsson, Martin"],["dc.contributor.author","Kalimo, Hannu"],["dc.contributor.author","Lannfelt, Lars"],["dc.contributor.author","Bayer, Thomas A."],["dc.date.accessioned","2018-11-07T08:48:00Z"],["dc.date.available","2018-11-07T08:48:00Z"],["dc.date.issued","2010"],["dc.description.abstract","The presence of A beta(pE3) (N-terminal truncated A beta starting with pyroglutamate) in Alzheimer's disease (AD) has received considerable attention since the discovery that this peptide represents a dominant fraction of A beta peptides in senile plaques of AD brains. This was later confirmed by other reports investigating AD and Down's syndrome postmortem brain tissue. Importantly, A beta(pE3) has a higher aggregation propensity, and stability, and shows an increased toxicity compared to full-length A beta. We have recently shown that intraneuronal accumulation of A beta(pE3) peptides induces a severe neuron loss and an associated neurological phenotype in the TBA2 mouse model for AD. Given the increasing interest in A beta(pE3), we have generated two novel monoclonal antibodies which were characterized as highly specific for A beta(pE3) peptides and herein used to analyze plaque deposition in APP/PS1KI mice, an AD model with severe neuron loss and learning deficits. This was compared with the plaque pattern present in brain tissue from sporadic and familial AD cases. Abundant plaques positive for A beta(pE3) were present in patients with sporadic AD and familial AD including those carrying mutations in APP (arctic and Swedish) and PS1. Interestingly, in APP/PS1KI mice we observed a continuous increase in A beta(pE3) plaque load with increasing age, while the density for A beta(1-x) plaques declined with aging. We therefore assume that, in particular, the peptides starting with position 1 of A beta are N-truncated as disease progresses, and that, A beta(pE3) positive plaques are resistant to age-dependent degradation likely due to their high stability and propensity to aggregate."],["dc.identifier.doi","10.1007/s00702-009-0314-x"],["dc.identifier.isi","000272464800012"],["dc.identifier.pmid","19823761"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?goescholar/4041"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21097"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Wien"],["dc.relation.issn","0300-9564"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Pyroglutamate Abeta pathology in APP/PS1KI mice, sporadic and familial Alzheimer's disease cases"],["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"]]

[["dc.bibliographiccitation.artnumber","13"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Molecular Neurodegeneration"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Guzmán, Erika A."],["dc.contributor.author","Bouter, Yvonne"],["dc.contributor.author","Richard, Bernhard C."],["dc.contributor.author","Lannfelt, Lars"],["dc.contributor.author","Ingelsson, Martin"],["dc.contributor.author","Paetau, Anders"],["dc.contributor.author","Verkkoniemi-Ahola, Auli"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Bayer, Thomas A."],["dc.date.accessioned","2019-07-09T11:39:41Z"],["dc.date.available","2019-07-09T11:39:41Z"],["dc.date.issued","2014"],["dc.description.abstract","Background According to the modified amyloid hypothesis the main event in the pathogenesis of Alzheimer’s disease (AD) is the deposition of neurotoxic amyloid β-peptide (Aβ) within neurons. Additionally to full-length peptides, a great diversity of N-truncated Aβ variants is derived from the larger amyloid precursor protein (APP). Vast evidence suggests that Aβx-42 isoforms play an important role triggering neurodegeneration due to its high abundance, amyloidogenic propensity and toxicity. Although N-truncated and Aβx-42 species have been pointed as crucial players in AD etiology, the Aβ5-x isoforms have not received much attention. Results The present study is the first to show immunohistochemical evidence of Aβ5-x in familial cases of AD (FAD) and its distribution in APP/PS1KI, 5XFAD and 3xTG transgenic mouse models. In order to probe Aβ5-x peptides we generated the AB5-3 antibody. Positive plaques and congophilic amyloid angiopathy (CAA) were observed among all the FAD cases tested carrying either APP or presenilin 1 (PS1) mutations and most of the sporadic cases of AD (SAD). Different patterns of Aβ5-x distribution were found in the mouse models carrying different combinations of autosomal mutations in the APP, PS1 and Tau genes. All of them showed extracellular Aβ deposits but none CAA. Additionally, they were all affected by a severe amyloid pathology in the hippocampus among other areas. Interestingly, neither 5XFAD nor APP/PS1KI showed any evidence for intraneuronal Aβ5-x. Conclusions Different degrees of Aβ5-x accumulations can be found in the transgenic AD mouse models and human cases expressing the sporadic or the familial form of the disease. Due to the lack of intracellular Aβ5-x, these isoforms might not be contributing to early mechanisms in the cascade of events triggering AD pathology. Brain sections obtained from SAD cases showed higher Aβ5-x–immunoreactivity in vascular deposits than in extracellular plaques, while both are equally important in the FAD cases. The difference may rely on alternative mechanisms involving Aβ5-x peptides and operating in a divergent way in the late and early onset forms of the disease."],["dc.identifier.doi","10.1186/1750-1326-9-13"],["dc.identifier.fs","603695"],["dc.identifier.pmid","24694184"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10042"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58023"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Abundance of Aß5-x like immunoreactivity in transgenic 5XFAD, APP/PS1KI and 3xTG mice, sporadic and familial Alzheimer´s disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]